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Welcome to our recap of the latest findings on myeloma treatments reported at the European Hematology Association meeting that kicked off Thursday in Madrid, Spain. Clinicians and researchers gathered to present and discuss several updates in multiple myeloma relating to:

Let us break down the key findings for you…

Antibody drug conjugate

Blenrep (Belantamab mafodotin)

On Thursday, a late-breaking abstract (Abstract: LBA3440) presented by researchers from Greece showed Blenrep in combination with Pomalyst (pomalidomide) and dexamethasone (Pd) lowered the risk of disease progression or death by 48% compared to Velcade (bortezomib) plus Pd. Results of the phase 3 DREAMM-8 trial, which included 302 patients who have tried at least one prior line of therapy, including Revlimid (lenalidomide), were presented a couple of weeks ago at the American Society of Clinical Oncology (ASCO) annual meeting and also published in the New England Journal of Medicine (Dimopoulos M, NEJM 2024).

Side effects of the combination of Blenrep with Pd (BPd) were consistent with previous clinical trials of Blenrep.

In a second abstract (Abstract: S214) on Blenrep , researchers from Spain presented data from the phase 3 DREAMM-7 study that showed Blenrep in combination with Velcade (bortezomib) and dexamethasone (BVd) more than doubled progression-free survival (PFS), that is the time until disease progression, compared to Darzalex (daratumumab) in combination with Vd (36 vs 13 months). Results of the trial, which included 494 patients who had received 1 or more prior lines of therapy but no prior treatment with an anti-BCMA therapy, were presented earlier at ASCO and published in the New England Journal of Medicine (Hungria V, NEJM 2024).

Side effects of the BVd were consistent with previous clinical trials of individual drugs. Most common side effects were low platelet counts, blurred vision, and dry eye. Eye problems were generally reversible and manageable with dose modifications. Despite the higher incidence of eye issues in patients who received BVd, overall patient-reported health-related quality of life did not differ substantially between the treatment groups over time.

Taken together, the results from the two clinical trials represent a second opportunity for Blenrep, which was taken off the US market in November of 2022 following the request of the U.S Food and Drug administration (FDA) as the phase 3 trial did not meet its primary endpoint. Blenrep was originally granted accelerated approval in August 2020, based on a single arm trial, by the FDA for relapsed/refractory patients who had received at least four prior treatments.

Results from these trials indicate that the original indication for Blenrep, which recommended administration once every three weeks at 2.5 milligrams per kilogram of body weight, had not been optimized for patients; these studies took a different approach, resulting in fewer side effects for patients. In DREAMM-8, the initial dose of Blenrep was the same, however subsequent doses were lowered to 1.9 milligrams per kilogram and administered every four weeks. Researchers noted that the dose reductions and the use of lubricating or moisturizing eye drops helped improve treatment outcomes in patients.

CD-38 Antibody Therapy

Darzalex (daratumumab)

New data continue to confirm that a four-drug combination for newly diagnosed patients is a new standard of care. In the primary analysis of the phase 3 PERSEUS trial, researchers showed that subcutaneous Darzalex in combination with Revlimid, (lenalidomide), Velcade (bortezomib), and dexamethasone (D-VRd) followed by Darzalex plus Revlimid (D-R) maintenance reduced risk of progression or death by 58 percent compared to VRd in patients with newly diagnosed multiple myeloma (NDMM) who received a stem cell transplant.

Researchers from the Netherlands presented additional data from the PERSEUS trial. Their analysis (Abstract: S201) of minimal residual disease (MRD) negativity—that is no disease was detected after treatment—showed that MRD negativity rates were higher with D-VRd compared to VRd for after 3 years (65% vs 30%).

The authors conclude that these results support a D-VRd quadruplet induction and consolidation regimen and D-R maintenance regimen as the standard of care for NDMM patients deemed eligible for a stem cell transplant.

Sarclisa (isatuximab)

Data from 2 abstracts presented at EHA 2024 showed that adding Sarclisa (isatuximab), which is in the same class of treatments as Darzalex, to RVd improves outcomes in patients with NDMM.

The BENEFIT trial showed Sarclisa (isatuximab) in combination with VRd (Isa-VRd) significantly increased the MRD negativity to 47% compared to 24% in patients who were treated with IsaRd, according to data presented by researchers in France (Abstract S202). The phase 3 BENEFIT study included patients aged 65-79 years with NDMM who were determined to be ineligible for a stem cell transplant.

In the next abstract (Abstract S203), German researchers revealed their interim analysis of the GMMG-HD7 trial, which demonstrated that the addition of Sarclisa to VRd (Isa-VRd) and high-dose therapy (melphalan) followed by stem cell transplant improved MRD negativity rates compared to VRd alone (72% vs 57%).

Findings from both studies further support the use of Isa-VRd as a new standard of care for patients with NDMM.

CAR T-cell Therapy in Earlier Lines of Therapy

Carvykti (ciltacabtagene autoleucel)

The first abstract (Abstract: S205) highlighted findings from an analysis of the CARTITUDE-2 study that evaluated Carvykti with or without Revlimid maintenance in patients who achieved less than a CR after transplant ASCT and frontline therapy.

Researchers from the Netherlands noted that a single infusion of Carvykti with or without Revlimid maintenance demonstrated deep and durable responses. Of the 17 patients treated with Carvykti 94% achieved an ORR, with 94% also achieving a CR or better. The safety profile was like prior trials of Carvykti with or without Revlimid maintenance. After 22 months of follow up, the most common side effects were low white blood cell counts, cytokine release syndrome (CRS) or flu-like symptoms, neurotoxicity, and infections.

Further studies, with a median follow up greater than 2 years, will continue to examine the potential role of CAR T-cell therapy in frontline treatment of patients.

Abecma (Idecabagene vicleucel)

Patients with MM who relapse early after induction therapy and stem cell transplant have a poor prognosis. In the pivotal phase 2 KarMMa study, treatment with Abecma resulted in frequent, deep, and durable responses in patients who were had received all major classes of treatments and no longer responded to their last treatment. Ongoing studies are evaluating the potential use of CAR T-cell therapy in earlier lines of therapy.

In the next abstract (Abstract: S208), French researchers reported that 94% of NDMM transplant-eligible patients whose disease progressed less than 18 months after receiving first line therapy achieved a response following a single infusion of Abecma. Of the 31 patients who received Abecma, low white blood cell counts, low platelet counts, CRS, and infections were the most common side effects.

Investigational CAR T-cell Therapy

CAR T cell therapies targeting B‑cell maturation antigen (BCMA) have resulted in unprecedented responses in RRMM; however, relapses are frequent, and the development of new approaches is needed. Four abstracts presented at EHA 2024 highlighted results from early phase clinical trials on investigational CAR T-cell therapies for NDMM and RRMM.

GC012F

GC012F is a new, dual-targeting CAR-T cell therapy that binds to BCMA and CD19 on myeloma cells and is manufactured within 24 hours of removal of plasma from a patient. Researchers from China colleagues reported their findings from an early phase trial that included 22 patients with high-risk NDMM who were eligible for a stem cell transplant-eligible (Abstract S200). Patients were considered high-risk if they had one or more of the following features: R-ISS-2 or-3; del17p, t(4;14), t(14;16), or 1q21amp; or extramedullary disease.

Following 23 months of follow up, the results showed all patients achieved a response and MRD negativity with GC012F. Low-grade CRS was the main side effect reported in this early phase study. The authors conclude that these promising preliminary results require further assessment of GC012F for NDMM with more patients and longer follow-up.

Equecabtagene autoleucel

Chinese researchers reported their findings from an early phase clinical trial that evaluated a single infusion of equecabtagene autoleucel in high-risk NDMM patients who were deemed ineligible for a stem cell transplant. Findings from their abstract (Abstract S206) showed that all 16 patients who received equecabtagene autoleucel achieved a response and were MRD negative 7 months after treatment. High-risk features were defined as one or more of the following: R-ISS-3; del17p, t(4;14), t(14;16), or 1q21amp; or extramedullary disease. The most common side effects were infections, CRS, and low white blood cell counts.

Anitocabtagene autoleucel

Findings from an early phase trial showed that all patients achieved a response and 89% achieved MRD negativity after one-year of receiving a single dose of anitocabtagene autoleucel. The abstract (Abstract S207), presented by Dr. Matthew Frigault and colleagues from Massachusetts General Hospital Cancer Center, included data from 38 patients with RRMM who had received 3 or more lines of prior therapy. Anitocabtagene autoleucel has a unique protein, called a D-Domain, that is designed to bind more firmly to BCMA and reduce the risk of side effects such as CRS. Researchers reported that CRS and neurotoxicity as the most common side effects observed with anitocabtagene autoleucel therapy.

Zevorcabtagene autoleucel (zevor-cel)

In this abstract (Abstract S209), researchers from China showed that 92% of patients with RRMM who received a single infusion of zevorcabtagene autoleucel achieved a response. The early phase study included 102 patients with RRMM who had received at least 3 prior lines of therapy. Researchers noted that CRS, neurotoxicity, and infections were the most common side effect observed.

Investigational Bispecific Antibodies

Cevostamab

Salvage therapies for patients who are refractory or relapse following BCMA-targeted therapy remains an urgent unmet need. Cevostamab, a bispecific antibody that targets the antigen FcRH5, has shown promising activity in heavily pretreated patients with RRMM in early phase clinical trials.

In this abstract (Abstract S210), Dr. Shaji Kumar and colleagues from the Mayo Clinic reported their findings from an early phase CAMMA 2 STUDY in 21 patients with RRMM whose disease no longer responds to the major classes of drugs and have received a prior BCMA-targeted agent, such as Blenrep or CAR T-cell therapy. The preliminary results showed that 67% of patients achieved a response with cevostamab.

Linvoseltamab

Linvoseltamab is another investigational BCMA-targeting bispecific antibody for patients with RRMM who previously received 3 or more prior treatments. With 14 months follow-up, Dr Suzanne Lentzsch and colleagues from Columbia University showed an overall response rate of 71% for patients receiving linvoseltamab.

Additional results from this abstract (Abstract S212) revealed that 67% of patients with high-risk cytogenetics achieved a response. Infections, CRS, and low white and red blood cells counts were the most common side effects observed in patients receiving linvoseltamab. The phase 3 trial, LINKER-MM3, will be initiated in patients with RRMM and could provide some insight on the clinical role of linvoseltamab.

ABBV-383

In the final abstract (Abstract S211) researchers from Germany reported that 60mg once weekly ABBV-383 monotherapy was the optimal therapeutic dose for patients with RRMM who received
3 or more prior lines of therapy, including All major classes of drugs. 65% of patients who received 60mg once weekly ABBV-383 monotherapy achieved a response. CRS, low white and red blood cells counts, as well as low platelet counts were the most common side effects observed in patients receiving ABBV-383.

The Phase 3 trial CERVINO was recently started and will evaluate the efficacy, safety, and tolerability of ABBV-383 monotherapy compared with standard available therapies in patients with RRMM who have received at least two lines of prior therapy.

Keep an eye out for MMRF updates from the 21st International Myeloma Society annual meeting in September!

Welcome to the final day of coverage from the latest advances on myeloma treatment presented at the American Society of Clinical Oncology (ASCO) meeting. Highlights from today featured updates on tocilizumab pretreatment to improve tolerability of the BCMA bispecific antibody Tecvayli (teclistamab), as well as investigational CAR T-cell therapy and maintenance therapy. Here’s a quick recap!

Tocilizumab Pretreatment

Tocilizumab has proven to be an effective treatment to lessen the impact of cytokine release syndrome (CRS), which presents as flu-like symptoms experienced by most patients who receive either CAR T-cell therapy or bispecific antibody treatment. Early phase trials suggest that tocilizumab could prevent the development of CRS without limiting the anti-myeloma activity of bispecific antibody therapy.

In the first abstract, (Abstract: 7517) researchers from the Netherlands reported their findings from an 8-month follow up of patients from a MajesTEC-1 cohort, investigating the use of tocilizumab pretreatment for the reduction of CRS in patients treated with Tecvayli. The data showed that a single dose of tocilizumab pretreatment reduced the risk of CRS in 24 patients with RRMM by 65%. In this study, tocilizumab was given by injection up to 4 hours before the first dose of Tecvayli was given.

Outpatient administration of Tecvayli is being examined in the early phase OPTec study. Early data (Abstract: 7528) from 10 patients showed that tocilizumab pretreatment 2 to 4 hours before the first dose of Tecvayli reduces the incidence of CRS and neurotoxicity.

These findings suggest that tocilizumab treatment before the first dose in a community clinic setting could reduce the need for patients to visit the hospital for drug administration and make Tecvayli more accessible for those who have limited treatment options. Further data from ongoing clinical trials with more patients will shed light on the potential role tocilizumab pretreatment could play in reducing the risk of CRS and improving treatment accessibility.

Investigational CAR T-cell Therapy

OriCAR-017

GPRC5D, a receptor expressed on multiple myeloma cells, has become a promising target for novel immunotherapeutic strategies such as bispecific antibodies and CAR T-cell therapy, especially for patients who no longer respond to BCMA-targeted therapies such as Tecvayli and Elrexfio (bispecific antibodies) as well as Abecma and Carvykti (CAR T-cell therapy options).

In this abstract (Abstract: 7511) , investigators from China presented their findings from an early phase trial evaluating OriCAR-017, a CAR T-cell therapy designed to specifically target GPRC5D, in patients with RRMM. After 2 years of follow up, all 10 patients who received a single infusion of OriCAR-017 responded to therapy, with 80% achieving a stringent complete response, and a 100% minimal residual disease negative rate—that is, no disease was detected after treatment—was confirmed 3 months after therapy. Low-grade cytokine release syndrome was the most common side effect reported.

Future studies will provide more information on the clinical potential of GPRC5D-targeted CAR T-cell therapy in RRMM.

Maintenance Therapy

Revlimid (lenalidomide) + Empliciti (elotuzumab)

Maintenance therapy with Empliciti (elotuzumab) and Revlimid (lenalidomide) may improve progression-free survival in patients with myeloma who recently underwent a stem cell transplant, according to recent results from an early phase trial. In addition, this combination maintenance therapy was safe and tolerable in patients, according to Dr. Sheeba Thomas and colleagues from the University of Texas MD Anderson Cancer Center.

Data from their abstract (Abstract: 7509) revealed that progression free survival (PFS)—that is, the length of time during and after treatment in which a patient is living with a disease that does not get worse—was 75 months. Most common side effects were low white blood cell counts, respiratory infections, diarrhea, and fatigue. Additional studies will help determine the role and potential benefit of this combination maintenance therapy.

Small Molecules

Venetoclax

Venetoclax is a potent and selective oral BCL-2 inhibitor with demonstrated anti-myeloma activity in patients with RRMM and a translocation of chromosomes 11 and 14 [t(11;14)]. The phase 3 CANOVA study evaluated the safety and efficacy of venetoclax plus dexamethasone (VenDex) for patients with t(11;14)-positive RRMM who have had at least two prior lines of therapy. The results showed numerically longer PFS compared with Pomalyst (pomalidomide) and dexamethasone (PomDex), though the difference was not statistically significant. The most common adverse events experienced by patients treated with VenDex included infection and diarrhea.

In the final abstract (Abstract 7510), researchers from Canada presented findings of their analysis of patient biomarkers—that is, substances like proteins, genes, and DNA that show the presence and severity of myeloma—to identify patients who may respond to treatment with VenDex. Patients with either normal 1q or (1q) gain—that is, the presence of one extra copy of DNA—had numerically improved PFS, ORR, and MRD negativity with VenDex compared to PomDex.

The findings suggest that treatment with VenDex can help patients with (1q) gain. Additional studies will help determine the potential role of VenDex and RRMM treatment.

Keep an eye out for MMRF updates from the annual European Hematology Association meeting later this month!

Welcome to the second day of our recap of the latest findings on myeloma treatments reported at the American Society of Clinical Oncology (ASCO) meeting. Monday featured updates on treatment options for newly diagnosed multiple myeloma (NDMM) patients, including quadruplet therapies, CAR T-cell therapy, and bispecific antibody therapy. Let us break down the key findings for you…

Quadruplet Therapies for NDMM

Sarclisa (isatuximab)

While three-drug induction regimens (that is, those containing a proteasome inhibitor such as Velcade or Kyprolis, an immunomodulatory agent – typically Revlimid, and dexamethasone) were once standard for NDMM, recent clinical trials have shown a clear benefit to adding an anti-CD38 monoclonal antibody such as Darzalex (daratumumab) as first-line therapy for myeloma patients, particularly prior to stem cell transplant.

In the first abstract (Abstract: 7500), researchers from France reported that Sarclisa (isatuximab) is the first anti-CD38 monoclonal antibody to significantly improve progression-free survival (PFS)—that is, the length of time during and after treatment in which a patient is living with a disease that does not get worse— in combination with VRd for newly diagnosed patients who were ineligible for a stem cell transplant.

Findings from the phase 3 IMROZ trial showed Sarclisa in combination with Velcade (bortezomib), Revlimid (lenalidomide), and dexamethasone (Isa-VRd) followed by Sarclisa-Rd reduced the risk of recurrence or death by 40% versus VRd followed by Rd. The safety profile was consistent with previous studies of the combination of Isa-VRd. Further details of the study of 446 patients were simultaneously published in the New England Journal of Medicine (Facon T, NEJM 2024).

The second abstract (Abstract: 7501) that reported updates from the phase 3 BENEFIT study of Isa-VRd versus IsaRd in patients aged 65-79 years with NDMM who were determined to be ineligible for a stem cell transplant. Researchers from France evaluated the prolonged use of bortezomib for 18 months with reduced intensity weekly schedule versus IsaRd.

Results showed that Isa-VRd significantly increased the minimal residual disease (MRD) negativity—that is no disease was detected after treatment—to 53% compared to 26% of patients who were treated with IsaRd. This benefit was observed as early as 12 months and was consistent across various subgroups, including those with high-risk cytogenetics or stage III disease. These trial findings were simultaneously published in Nature Medicine (Leleu X, Nat Med 2024).

Findings from both of these studies further support the use of Isa-VRd as a new standard of care for patients with NDMM.

Darzalex (daratumumab)

In the next abstract (Abstract: 7502), researchers from Spain reported updated results from the Phase 3 PERSEUS study that showed the anti-CD38 monoclonal antibody Darzalex (daratumumab) in combination with Velcade (bortezomib), Revlimid (lenalidomide), and dexamethasone (D-VRd), followed by a maintenance regimen of subcutaneous Darzalex plus Revlimid (D-R) demonstrated superior PFS and increased depth of response compared to VRd induction and R maintenance in newly diagnosed patients.

The recent analysis showed deeper responses and higher rates of MRD over time in 355 patients treated with D-VRd + D-R compared to 354 patients treated with VRd + R.

The researchers reported that the rates of deep and sustained MRD negativity were associated with improved progression-free survival (PFS)—that is, the length of time during and after treatment in which a patient is living with a disease that does not get worse— with Darzalex-based quadruplet regimen in these patients.

Results from the primary analysis of the PERSEUS study were published earlier this year in The New England Journal of Medicine (Sonneveld P, 2024).

The authors concluded that these data further support D-VRd and D-R maintenance as a new standard of care for newly diagnosed patients.

CAR T-cell Therapy for NDMM

Carvykti (ciltacabtagene autoleucel)

The first abstract (Abstract: 7505) highlighted findings from an analysis of the CARTITUDE-2 study that evaluated Carvykti with or without Revlimid maintenance in patients who achieved less than CR after transplant ASCT and frontline therapy.

Researchers from France noted that a single infusion of Carvykti with or without Revlimid maintenance demonstrated deep and durable responses. Of the 17 patients treated with Carvykti 94% achieved an ORR, with 94% also achieving a CR or better. The safety profile was similar to prior trials of Carvykti with or without Revlimid maintenance. After 22 months median follow up, most common side effects were low white blood cell counts, cytokine release syndrome (CRS) or flu-like symptoms, neurotoxicity, and infections.

Further studies, with a median follow up greater than 2 years, will continue to examine the potential role of CAR T-cell therapy in frontline treatment of patients.

In the next abstract, Dr Luciano Costa and colleagues reported Abstract: 7504 that Carvykti as second-line therapy significantly improved PFS and deepened responses versus two standard therapies for patients with functional high-risk multiple myeloma—that is patients whose disease progressed either after the start of frontline treatment or 18 months following a transplant. This patient population is known to have poor prognosis, and yet has not been well represented in prior clinical trials.

Patients treated with Carvykti compared to the standard of care [that is, either Pomalyst (P) + Vd or Dara-Pd until disease progression] had higher overall response rates (90% vs 79%), complete response or better (71% vs 35%), and MRD negativity (63% vs 19%). Researchers noted that similar results were observed in functional high-risk patients.

CRS and neurotoxicity with Carvykti was comparable among other clinical trials of patients who received Carvykti versus standard therapies as second-line treatment. The researchers conclude that Carvykti could benefit patients with functional high-risk multiple myeloma.

Bispecific Antibody for NDMM

Tecvayli

Tecvayli is the first “off-the shelf” BCMA-targeted bispecific antibody approved for patients with heavily pretreated RRMM. In this abstract (Abstract: 7506), French researchers presented the first results of a single-arm (that is, no treatment comparison group) from the phase 3 MajesTEC-7 study that evaluated Tecvayli in combination with Darzalex and Revlimid (Tec-DR) in NDMM patients who were deemed ineligible for stem cell transplant. The authors reported an overall response rate for Tec-DR was 92%, with 73% achieving a very good partial response or better. Infections (96%) and CRS (62%) or flu-like symptoms, were the most common side effects reported—all of which resolved, according to the authors.

We look forward to additional data from this and other clinical trials investigating Tecvayli-containing regimens in the upfront treatment setting.

Small Molecules for NDMM

All-oral triplet: iberdomide, Ninlaro (ixazomib), and dexamethasone

Currently, DRd or VRd are considered standard treatment options for NDMM patients who were deemed ineligible for stem cell transplant. However, many elderly (that is, adults 70 years or more) or frail patients do not respond to upfront therapy and new treatment options with improved activity are needed.

Iberdomide is a novel, potent oral cereblon E3 ligase modulator (CELMoD™), which is similar to but more potent than Revlimid, with a dual function: activate the immune system and directly kill myeloma cells by inducing the destruction of proteins that drive cancer growth. In prior trials, iberdomide has demonstrated promising activity in MM patients refractory to Revlimid or Pomalyst.

In the final abstract (Abstract 7507), researchers from France presented their findings on an all-oral triplet iberdomide, Ninlaro (ixazomib), a proteasome inhibitor, and dexamethasone in elderly patients with myeloma after 1 prior line of therapy.

The researchers found that overall response rate was 65% and 52% did not experience disease progression one year after treatment with the all-oral regimen. Response rates and PFS were maintained in frail patients and those who were refractory to DRd or VRd. Most common side effects were low white blood cell counts, infections, and numbness or tingling in hands, arms, or feet.

Additional studies will continue to examine the potential role of an all-oral triplet regimen of iberdomide, Ninlaro, and dexamethasone in elderly or frail patients with myeloma after 1 prior line of therapy.

Be sure to tune in tomorrow for our final recap of clinical trial data presented at the annual ASCO meeting.

Welcome to the first day of our recap of the latest findings on myeloma treatments reported at the American Society of Clinical Oncology (ASCO) meeting that kicked off Friday in Chicago. This weekend gave us important updates on the use of Blenrep (belantamab mafodotin), a type of treatment called an antibody drug conjugate (ADC) that targets the protein BCMA, in patients with relapsed/refractory multiple myeloma (RRMM).

On Saturday, researchers from Spain presented from the phase 3 DREAMM-7 study that showed Blenrep in combination with Velcade (bortezomib) and dexamethasone (BVd) more than doubled progression-free survival (PFS), that is the time until disease progression, compared to Darzalex (daratumumab) in combination with Vd (36 vs 13 months). Results of the trial, which included 494 patients who had received 1 or more prior lines of therapy but no prior treatment with an anti-BCMA therapy, was simultaneously published in the New England Journal of Medicine (Hungria V).

Side effects of the BVd were consistent with previous clinical trials of individual agents. Most common side effects were low platelet counts (69%; 55% were severe grade), blurred vision (66%; 22% were severe grade), and dry eye (51%). Eye toxicity was generally reversible and manageable with dose modifications. Despite the higher incidence of eye toxicity in patients who received BVd, overall patient-reported health-related quality of life did not differ substantially between the treatment groups over time.

On Sunday, a late-breaking abstract (Abstract LBA105) presented by Canadian researchers showed Blenrep in combination with Pomalyst (pomalidomide) and dexamethasone (Pd).   lowered the risk of disease progression or death by 48% compared to Velcade (bortezomib) + Pd Results of the phase 3 DREAMM-8 trial, which included 302 patients who have tried at least one prior line of therapy, including Revlimid (lenalidomide), were simultaneously published in the New England Journal of Medicine (Dimopoulos M, NEJM 2024).

Side effects of the combination of Blenrep with Pd (BPd) were consistent with previous clinical trials of Blenrep.

Taken together, the results from the two clinical trials represent a second opportunity for Blenrep, which was taken off the US market in November of 2022 following the request of the U.S Food and Drug administration (FDA). This request was based upon the previously announced outcome of the DREAMM-3 phase 3 confirmatory trial which did not meet the requirements of the FDA Accelerated Approval regulations. Blenrep was originally granted accelerated approval in August 2020 by the FDA for relapsed/refractory patients who had received at least four prior treatments.

Results from these trials indicate that the original indication for Blenrep, which recommended administration once every three weeks at 2.5 milligrams per kilogram of body weight, had not been optimized for patients; these studies took a different approach, resulting in fewer side effects for patients. In DREAMM-8, the initial dose of Blenrep was the same, however subsequent doses were lowered to 1.9 milligrams per kilogram and administered every four weeks. Researchers noted that the dose reductions and the use of lubricating or moisturizing eye drops helped improve treatment outcomes in patients.

Stay tuned tomorrow for additional updates from trials evaluating treatment of patients with newly diagnosed and relapsed/refractory disease.

On April 12, the FDA Oncologic Drugs Advisory Committee, or ODAC, met with leading multiple myeloma key opinion leaders (KOLs) and other stakeholders to discuss the topic of minimal residual disease, or MRD, as a clinical endpoint. Two groups, the Sylvester Comprehensive Cancer Center of Miami FL, led by Dr. Ola Landgren, and the i2TEAMM, led by Drs. Brian Durie (IMF) and Nikhil Munshi (DFCI), presented data from separate meta-analyses (meaning data from numerous previous studies that are combined to produce a summary study that is more likely to have statistically significant results) of previous clinical trials where MRD was measured at specific timepoints and then correlated to progression free survival (PFS) and overall survival (OS). These meta-analyses together involved 42 clinical trials and 21,006 patients in total.  Specifically, the question the ODAC discussed and voted on was “Does the data presented support the use of MRD as an intermediate clinical endpoint for accelerated drug approval in multiple myeloma?”

As a bit of background, the MMRF, in collaboration with Dr. Landgren and the FDA, has been supporting yearly meetings on this topic since 2014. There is a clear need for new therapies in myeloma, and with new immunotherapies currently lengthening the lives of patients and improving overall response rates (ORR), it has become more difficult to accumulate significant PFS data in trials in a reasonable timeframe, which is currently required for FDA approval; this can sometimes take up to 10 years, and many patients are unable to wait that long for new effective therapies to be approved. Using MRD measurement at a specific timepoint in a trial, 9 months and/or 12 months (+/- 3 months) after treatment is initiated, may provide assessment of sustained MRD, which is a hallmark of deep response to the clinical regimen.

After careful presentation of the data by both groups and an extended discussion with the FDA of the take-aways from the data, the ODAC panel voted 12-0 in favor of the use of MRD as an intermediate endpoint to support accelerated approval. What this means:

MRD testing may become more commonplace, but for now is mainly available only in major academic medical centers. For more information about this topic or anything else myeloma-related, please contact our patient navigators at 1-888-841-6673, Mon-Fri 9AM – 7PM ET, or by email at [email protected].

Norwalk, Conn., November 30, 2023 — The Multiple Myeloma Research Foundation (MMRF) announced today the first recipients of its Scholars Program to improve equity in myeloma research and overall outcomes by increasing workforce diversity.  

Awardees Eden Biltibo, MD, MS, Assistant Professor at Vanderbilt University Medical Center, and Joselle Cook, MBBS, Assistant Professor at Mayo Clinic Rochester, will each be awarded up to $100,000 per year for four years to support their career development to first-tenure track positions. The Scholars Program is an annual initiative from the MMRF, with support from Pfizer and GSK, to provide grant funding for Black researchers and clinicians (MD and/or PhD) who are currently active or interested in pursuing a research and/or clinical career in the field of myeloma.  

“Multiple myeloma is a disease that disproportionately affects Black people and we are committed to ensuring that researchers and clinicians within the field more closely represent this patient population,” said Michael Andreini, President and CEO at the MMRF. “Dr. Biltibo and Dr. Cook’s work will add tremendous value to our field to advance understanding and treatment of myeloma across diverse patient communities.”

Black patients make up 20 percent of the approximately 35,000 people diagnosed with myeloma annually in the United States. Despite the high incidence of myeloma in the Black community, most Black patients are diagnosed later when compared to other patient populations, and increases in survival rates for Black patients have not kept pace with improved survival rates seen in other patient populations. Black patients are also underrepresented in the research and clinical studies that are driving new treatments, accounting for only 5 percent of clinical trial participants in the United States. In addition, Black researchers and clinicians are significantly underrepresented in hematology-oncology, comprising less than 4 percent of oncology fellows and only 3 percent of medical oncologists in the United States. Through initiatives like the Scholars Program, the MMRF is committed to improving diversity and inclusion in the research and clinical fields to drive health equity for all patient groups with myeloma. 

About the Research Scholar Awardee Grants 

Dr. Biltibo’s proposal entitled, “Identifying Effective and Cost-Conscious Maintenance Daratumumab Dosing,” focuses on equitable, utilization of immunotherapeutics in multiple myeloma and improving racial diversity of clinical trial participants in the same field. She will lead a single-arm phase II, non-inferiority clinical trial that will compare the 2-year MRD-negativity rate of subcutaneous 8-weekly DARZALEX® (daratumumab) and daily REVLIMID® (lenalidomide) maintenance therapy with 4-weekly DARZALEX® (daratumumab) and daily REVLIMID® (lenalidomide) maintenance therapy using a historical treatment cohort from the GRIFFIN trial.

Dr. Cook’s proposal entitled, “Prevalence of MGUS Among Unique Populations of Black People,” will determine the prevalence of monoclonal gammopathy of undetermined significance (MGUS), a precursor disease to multiple myeloma, among East African people in Minnesota and an Afro-Caribbean population in Trinidad.  She will lead a team that will use modern tools such as mass spectrometry to identify the presence of monoclonal protein. For those with positive MGUS tests, genome wide association studies and single nucleotide polymorphism (SNP) analysis will be performed to determine ancestral origins and correlate with the prevalence of SNPs known to be associated with higher prevalence of certain IgH translocations.

About Multiple Myeloma 

Multiple myeloma is the second most common blood cancer in the US. It develops in the bone marrow and can spread throughout the body. In 2023, multiple myeloma is expected to be diagnosed in more than 35,000 Americans and take the lives of 12,000. Despite advances, most patients relapse and there is still no cure. Multiple myeloma is twice as common in the Black community compared to other ethnicities and the outcomes for Black patients are generally worse than that of white patients.  

About the Multiple Myeloma Research Foundation  

The Multiple Myeloma Research Foundation (MMRF) is the largest nonprofit in the world solely focused on accelerating a cure for each and every multiple myeloma patient. We drive the development and delivery of next-generation therapies, use data to drive optimal and more personalized treatment approaches, and empower myeloma patients with information and resources to extend their lives. Central to our mission is our commitment to advancing health equity so that all myeloma patients can benefit from the scientific and clinical advances we pursue. Since our inception, the MMRF has committed over $500 million for research, opened nearly 100 clinical trials, and helped bring 15+ FDA-approved therapies to market, which have tripled the life expectancy of myeloma patients. To learn more, visit www.themmrf.org.

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Multiple Myeloma Research Foundation Media Contact:

C.J. Volpe, Director, PR and Communications
203-652-0453
[email protected]

There have been important strides in multiple myeloma treatment in recent years including a striking series of new immune agents approved and progress in understanding the complex underlying disease biology. These gains are welcome achievements for the entire myeloma community – patients, families, healthcare providers, and researchers from industry and academia. Yet there is much more to do. Despite these and other advances, there is no cure for myeloma and most patients die of their disease. Some patients get very little benefit from this progress and long-term survivorship often involves protracted treatment and varied toxicities, including financial trauma.

The way forward requires even more collaboration. New forms of teamwork offer the possibility of new findings far beyond what individual groups could achieve alone. As in many endeavors, collaboration can still be elusive, particularly when there is little incentive to band together and a tendency to “go it alone” even in lethal diseases like myeloma. This is why intervention by, and funding from, organizations like the Multiple Myeloma Research Foundation (MMRF) is so critical. For the last twenty-five years, the MMRF has facilitated collaborative efforts to drive ambitious clinical studies that could not be done by any single institution. We have directed attention and dollars to find new insights about how myeloma starts as well as how it evolves to resist therapy.

With 2024 nearly upon us, the MMRF is again investing in new research challenges and new approaches to team building and collaboration. We recently announced that our MMRF Myeloma Accelerator Challenge (MAC) Program will invest $21 million over three years to focus on the biology of high-risk newly diagnosed multiple myeloma and the definition of high-risk smoldering precursor disease. This is a global research program comprised of three multi-institution partnerships across 18 different medical centers in the US, the Netherlands, Spain, Italy, and Germany:

Worldwide, the annual incidence of myeloma is currently 160,000 and the mortality rate is 106,000. We are excited about the results that will emerge from these MAC Program projects and the promise to change these numbers. Personally, I am pleased that these centers and the MMRF can work together to pool resources in a less common but lethal cancer, and study hundreds of patient samples from high-risk subsets of the disease. This approach will create new possibilities and advance compelling hypotheses on the path to rapid testing in clinical trials. This can result in better clinical strategies and more effective treatments, a critical step in the MMRF’s urgent pursuit of a cure for each and every myeloma patient.

Clearly there is more to do but there is no doubt we will be successful faster when we do this together.

2023 Accelerator Magazine

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Norwalk, Conn., November 2, 2023 — The Multiple Myeloma Research Foundation® (MMRF®) announced today the recipients of three $7 million MMRF Myeloma Accelerator Challenge (MAC) Program Grants totaling $21 million. Each of these three-year multicenter translational projects aim to foster collaboration and advance compelling hypotheses that are ready for rapid testing in clinical trials, a critical step in the MMRF’s urgent pursuit of a cure for each and every myeloma patient.

“The MMRF makes significant strategic investments to generate robust molecular and clinical data and deliver translational research that drives better treatment options for patients,” said George Mulligan, PhD, Chief Scientific Officer at the MMRF. “These MAC Grants are a critical new part of this investment, and we are excited that the programs selected will bring together multiple centers to work in highly collaborative networks. Our strategic plan identifies specific research areas that need more attention and only through multi-center collaboration can we rapidly create a large set of patients and samples suitable for new research methods.”

The MAC Grants are focused on two critical areas of unmet need in myeloma and are part of the MMRF’s strategic priority to drive optimal treatment approaches for patients. The first is optimizing first-line therapy for high-risk newly diagnosed multiple myeloma because high-risk patients often relapse early and show inferior survival compared to standard-risk patients. The next is improving identification of high-risk smoldering multiple myeloma (HR SMM); smoldering multiple myeloma is an early, asymptomatic stage that can progress to active multiple myeloma. For each research topic, the pooling of resources and samples across a network of institutions dramatically improves the ability to drive meaningful results.

“The pace of research needs to accelerate if we are to address the significant unmet needs in multiple myeloma, and the way forward will take collaboration and funding,” said Michael Andreini, President and CEO at the MMRF. “Bringing together diverse teams through our MAC Grants that normally have many barriers to working together will bring greater focus and scale to these research priorities, yielding more timely and impactful insights for patients.”

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About the MAC Grant Networks

Clinical & Multi-Omics Platforms to Define High-Risk Smoldering Multiple Myeloma.

Sagar Lonial, MD, Winship Cancer Institute of Emory University, is leading a network of institutions including Atrium Health Levine Cancer Institute, Icahn School of Medicine at Mount Sinai, Massachusetts General Hospital, Mayo Clinic, Memorial Sloan Kettering Cancer Institute, and Dana-Farber Cancer Institute. This team will develop an improved definition of high-risk SMM through the generation and analysis of new SMM patient data. These include use of cutting-edge technologies and a large, collaborative set of patient samples, with the goal of better defining which patients are suited for early intervention, which types of interventions can have the greatest impact, and which patients can safely be observed due to a low risk of disease progression.

A Systems Biology Approach to High-Risk Multiple Myeloma.

Prof. Pieter Sonneveld, MD, PhD, Erasmus Medical Center, is leading a European network of institutions including Erasmus Medical Center in Rotterdam, Amsterdam University Medical Centers, Julius Maximilian University of Würzburg, University of Turin, and the University of Salamanca. This team will investigate what makes less responsive, high-risk patients different from other patients with multiple myeloma. By combining different aspects of the disease, researchers will compile an integrated definition of high-risk multiple myeloma, a key step towards new treatments specifically designed for these patients.

 Transforming Treatment of High-Risk Myeloma.

Samir Parekh, MD, the Tisch Cancer Center at Mount Sinai, is leading a network of institutions including Albert Einstein Medical College, Hackensack University Medical Center, Stanford University Medical Center, University of California San Francisco, and Washington University of St. Louis. Using cutting-edge technologies, this team will analyze a large cohort of patient samples at the genomic and immune level to understand the critical events that drive high-risk multiple myeloma. The studies have the potential to identify new vulnerabilities that will be further studied using CRISPR gene editing in the laboratory.

About Multiple Myeloma

Multiple myeloma is the second most common blood cancer in the US. It develops in the bone marrow and can spread throughout the body. In 2023, multiple myeloma is expected to be diagnosed in more than 35,000 Americans and take the lives of 12,000. Despite advances, most patients relapse and there is still no cure. Multiple myeloma is twice as common in the Black community compared to other ethnicities and the outcomes for Black patients are generally worse than that of white patients.

About the Multiple Myeloma Research Foundation

The Multiple Myeloma Research Foundation (MMRF) is the largest nonprofit in the world solely focused on accelerating a cure for each and every multiple myeloma patient. We drive the development and delivery of next-generation therapies, use data to drive optimal and more personalized treatment approaches, and empower myeloma patients with information and resources to extend their lives. Central to our mission is our commitment to advancing health equity so that all myeloma patients can benefit from the scientific and clinical advances we pursue. Since our inception, the MMRF has raised over $500 million for research, opened nearly 100 clinical trials, and helped bring 15+ FDA-approved therapies to market, which have tripled the life expectancy of myeloma patients. To learn more, visit www.themmrf.org.

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Multiple Myeloma Research Foundation Media Contact:

C.J. Volpe, Director, PR and Communications
203-652-0453
[email protected]

20-year industry veteran to lead development, execution of MIF investment strategy

Norwalk, Conn., Oct. 5, 2023 — The Multiple Myeloma Research Foundation® (MMRF®) has announced the appointment of Stephanie Oestreich, Ph.D., MPA, as Managing Director of its venture philanthropy subsidiary, the Myeloma Investment Fund® (MIF®). In this role, Dr. Oestreich will lead the overall execution of the MIF’s investment strategy and serve as a member of the MMRF executive leadership team.

“We are thrilled to have Dr. Oestreich join our team as Managing Director of the MIF,” said Michael Andreini, President and CEO, the MMRF. “The MIF invests in the most promising companies that are developing innovative clinical assets and technologies that could be transformative for myeloma patients. Dr. Oestreich brings a wealth of business development experience in biopharma and biotech that will play an invaluable role in the continued growth and impact of our fund.”

Dr. Oestreich has more than 20 years of diverse experience in business development and strategic alliances spanning large biopharma, biotech, and early academic research. Previously, she served as Chief Business Officer at the biotech Galecto and Vice President at the cell therapy company Mnemo Therapeutics. In addition, Dr. Oestreich was a Venture Partner at RA Capital and Executive Vice President at Evotec, where she built its North American investment arm and started an incubator with Samsara BioCapital. Her experience also includes work at F. Roche Hoffmann-La Roche Ltd., where she served as International Business Leader, and Novartis in Business Development and in Commercial. 

“The MMRF has made a tremendous impact to help advance new therapies for myeloma patients and I am truly excited to join this effort as Managing Director of the MIF,” said Dr. Oestreich. “Through the MIF’s investment strategy, we will continue our work to advance the development of novel treatments and innovative therapeutic strategies for patients.”

In addition to her role at the MIF, Dr. Oestreich currently serves on the boards of the German American Business Council in Boston and the Harvard Kennedy School’s Women’s Network and is the chair of the McCloy Alumni Association. She is also on the faculty of MIT, a member of the Launchpad Venture Group, an advisor at grIP Venture Studio to Biognosys (a Bruker company), Invitris, CART company CelineTx, and to the drug development and investment company Orange Grove Bio. She is also a member of the W20 Entrepreneurship task force, the official engagement group of the G20. 

To learn more about the MIF, visit www.myelomainvestmentfund.org.

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About the Myeloma Investment Fund (MIF)

The Myeloma Investment Fund (MIF) is a venture philanthropy fund that invests in promising companies, clinical assets, and technologies in oncology to drive the development of new therapies for multiple myeloma. The MIF collaborates closely with portfolio companies to help them advance multiple myeloma research. This evergreen fund is supported entirely by philanthropy; all profits will be reinvested back into research for more effective treatments until there is a cure for every patient. For more information, visit www.myelomainvestmentfund.org.

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About the Multiple Myeloma Research Foundation (MMRF)
The Multiple Myeloma Research Foundation (MMRF) is the largest nonprofit in the world solely focused on accelerating a cure for each and every multiple myeloma patient. We drive the development and delivery of next-generation therapies, leverage data to identify optimal and more personalized treatment approaches, and empower myeloma patients and the broader community with information and resources to extend their lives. Central to our mission is our commitment to advancing health equity so that all myeloma patients can benefit from the scientific and clinical advances we pursue. Since our inception, the MMRF has committed over $500 million for research, opened nearly 100 clinical trials, and helped bring 15+ FDA-approved therapies to market, which have tripled the life expectancy of myeloma patients. To learn more, visit www.themmrf.org.

###

Multiple Myeloma Research Foundation Media Contact:

C.J. Volpe, Director, PR and Communications
203-652-0453
[email protected]