Management of patients with relapsed/refractory multiple myeloma (RRMM) is particularly challenging, as RRMM is characterized by genetic and cytogenetic alterations that drive resistance and result in progressively shorter durations of remission to each subsequent salvage therapy. Patients who relapse or are refractory to three or more lines of therapy that include a proteasome inhibitor (PI) or immunomodulatory drug (IMiD) have a median overall survival (OS) of less than 8 months, highlighting a need for improved treatment options for this patient population.
The therapeutic landscape for RRMM has grown considerably in recent years, with an expanding repertoire of agents now, or soon to be, available to improve outcomes for these patients. At the 64th American Society of Hematology (ASH) Annual Meeting and Exposition, held December 10–13 in New Orleans, Louisiana, clinical updates on CAR T-cell therapy, bispecific antibodies, and the monoclonal antibody isatuximab were presented, along with a preview of two new agents in different drug classes. The MMRF was there to capture this information and is pleased to share it here with the broader myeloma community.
CAR T-cell Therapy: How It’s Going
Depth of Response, Real-World Outcomes, Cytopenias
A study investigated the prognostic value of depth of response following CAR T-cell therapy. Minimal residual disease (MRD) was assessed by next-generation flow (NGF) and next-generation sequencing (NGS; 1 × 10-6 sensitivity) at 1, 3, 6, and 12 months after idecabtagene vicleucel (ide-cel) infusion. At months 1, 3, 6, and 12, the results showed:
- Concordant MRD status between NGF and NGS of 67%, 75%, 81.5%, and 73% following ide-cel infusion, with similar prognostic value at all time points
- Stringent complete response (sCR) rates of 11%, 23%, 26%, and 23%
- MRD negativity rates of 41%, 45%, 35%, and 18% (42%, 47%, 38%, and 19.5% at 1 × 10-5 sensitivity)
No differences in progression-free survival (PFS) were noted in patients with complete response (CR) or <CR 1 month after ide-cel infusion (8 vs 11 months, P=0.09; however, MRD positivity at 1 month predicted poor PFS compared to patients who achieved MRD negativity (median PFS 2 vs 11.5 months, P<0.001). At 3, 6, and 12 months post ide-cel infusion, patients who achieved CR and MRD negativity had longer median PFS than patients who achieved <CR and MRD negativity (P≤0.007). At 12 months post ide-cel, the median PFS for patients who are in CR/MRD negativity vs <CR/MRD negativity was 18 vs 6 months. For patients who were CR/MRD positive vs <CR/MRD positive, median PFS was 2 vs 0.3 months. Achieving sustained undetectable MRD after ide-cel is associated with prolonged PFS, and only MRD status—not CR status—predicted early relapse 1 month after ide-cel. Nevertheless, both MRD and CR status at 12 months were required to identify patients with longer PFS.
Eleven US academic centers conducted a retrospective analysis on the real-world outcome for patients treated with ide-cel after having previously received BCMA-targeted therapy. This patient profile had been excluded from the KarMMa-1 study that led to ide-cel approval. The total cohort of patients who received ide-cel was 193 patients, of whom 50 previously received BCMA-targeted therapy that included antibody-drug conjugates (ADCs; n=38, overall response rate [ORR] prior to ide-cel 17%); bispecific antibodies (n=7, ORR 0%); and CAR T-cell therapy (n=5, ORR 80%).
Patients who received prior BCMA-targeted therapy were more likely to have t(4;14) as a high-risk disease feature (23% vs 8%, P=0.005), a higher median number of prior lines of therapy (9 vs 6, P<0.0001), and penta-refractor disease (62% vs 37%, P=0.002) than were patients who had not received prior BCMA-targeted therapy. Patients who received prior BCMA-targeted therapy had a lower ORR to ide-cel (78% vs 88%, P=0.021) and ≥CR rate (29% vs 48%, P=0.018) than patients who did not receive prior BCMA-targeted therapy. Patients who had received BCMA-targeted treatment >6 months prior to receiving ide-cel had better outcomes than patients who received it <6 months prior, but this did not reach statistical significance: ORR, 83% vs 60% (P=0.076); CR rate, 34.5% vs 20% (P=0.22), and median PFS, 5.3 vs 3.0 months (P=0.39).
Prior BCMA-targeted treatment was associated with shorter median PFS than no prior treatment (3.2 vs 9 months, P=0.0002). The 3-month PFS rates were 57.2% for prior ADC, 41.5% for prior bispecific antibody, 77.8% for prior CAR T, and 85% for no prior BCMA-targeted treatment. The toxicity profile was consistent between patients who had or had not received prior BCMA-targeted treatment and consistent with KarMMa-1 results (grade ≥3 cytokine release syndrome [CRS] 2.0% and immune effector cell-associated neurotoxicity syndrome [ICANS] 8.5%). Results suggest that prior BCMA-targeted treatment is associated with inferior PFS and a trend toward inferior outcomes for patients receiving ide-cel within 6 months of having received prior BCMA-targeted therapy, warranting further investigation into the optimal timing of ide-cel infusion.
Cytopenias are a common side effect with the use of CAR T-cell therapy. Investigators at Mt. Sinai conducted a retrospective review of data from 90 patients with RRMM to determine the prevalence, severity, and underlying mechanisms of cytopenias following BCMA-targeted CAR T cell therapy as part of a clinical trial.
At days 0, 60, 120, 180, and 360, the researchers recorded the following:
- ≥Grade 3 cytopenia (anemia, thrombocytopenia, neutropenia) occurred in 39%, 33%, 28%, 13%, and 7% of patients
- ≥Grade 3 bicytopenia or pancytopenia (two or more lineages affected) occurred in 14%, 19%, 10%, 6%, and 2% of patients
Four months after CAR T-cell infusion, 28% of patients were considered to have “poor” (one or more persistent ≥grade 3 cytopenias) and 72% had “adequate” (normal or less-severe cytopenias) hematologic recovery. Patients with a poor recovery (compared with adequate recovery) were older (67 vs 60, P=0.01), more heavily pretreated (median number of prior lines of therapy 6 vs 4, P=0.04), and more likely to have received ≥1 autologous stem cell transplant (ASCT; 37% vs 13%, P=0.04). Implications from this study are that reduced bone marrow reserve due to aging or treatment-related toxicity may contribute to decline in hematopoietic function in RRMM patients.
Options After Failure
Despite rapid and deep responses with CAR T-cell therapy, patients eventually relapse. A number of studies are looking at outcomes and options for patients post-CAR T therapy. University of California, San Francisco investigators conducted a retrospective analysis of 78 patients with RRMM who received BCMA-targeted CAR T-cell therapy. Median age of patients was 64.5 years, median prior lines of therapy was 7, 59% had high-risk cytogenetics (including 1q gain), and 64% were triple-class refractory (28% penta-drug refractory). Most patients (79%) achieved a very good partial response (VGPR) or better (64% achieved MRD negativity), median PFS was 13 months, and median OS was 31.4 months. The presence of 1q copy number gain was associated with worse OS. No OS differences were observed between patients with high-risk (HR) vs standard risk (SR) cytogenetics (based on the Revised-International Staging System [R-ISS]). Progression after CAR T-cell therapy was seen in 42 patients; 88% of these patients received ≥1 subsequent salvage therapy (median 3 lines of therapy). Subsequent therapies included BCMA CAR T, BCMA bispecific antibodies, anti-CD38 antibodies, alkylators, PIs, or IMiDs. The overall response rate was 75%, 60%, 52.6%, 46.3%, 40.6%, and 37.5%, respectively. Patients who had previously been refractory to a specific drug class re-responded after CAR T relapse. Median OS after progressing on CAR T was 14.8 months and 18 months for patients who received subsequent BCMA CAR T or BCMA bispecific antibodies within 6 months of progressing on CAR T.
Use in Earlier Line of Treatment
The phase 2 multicenter KarMMa-2 study is investigating the use of ide-cel in 37 patients who have RRMM and are considered to have high-risk disease (defined as early relapse after frontline therapy or inadequate response after frontline ASCT). Patients received a single infusion of ide-cel at 150-450 × 106 CAR+ T cells. Most patients were refractory to an IMiD (86.5%) or a PI (89.2%), and 86.5% had double-refractory disease. Median follow up is 21.5 months, and the ORR was 83.8% (CR rate 45.9%). MRD negativity was achieved in 85% and 70% of evaluable patients at 6 months and 12 months, respectively, post-ide-cel infusion. MRD negativity was sustained (≥18 months) in five patients. Median duration of response was 15.7 months, median PFS was 11.4 months, and median OS was not reached. Neutropenia occurred in 94.6% of patients, anemia in 45.9%, and thrombocytopenia in 37.8%. Two patients died due to pneumonia and pseudomonal sepsis. CRS (grade 1/2) occurred in 81.1% of patients, and 1 patient had a grade 3 event. Neurotoxicity (grade 1/2) occurred in 21.6% of patients (none had ≥grade 3). These results suggest a benefit to use of ide-cel in earlier lines of treatment.
Isatuximab-pomalidomide-dex is approved for RRMM patients who have received at least two prior treatments (including lenalidomide and a PI) based on data from the ICARIA-MM phase 3 trial (isatuximab-pomalidomide-dex [Isa-Pd] vs pomalidomide-dex [Pd]). Clinicians at the Dana Farber Cancer Institute provided an updated, long-term efficacy report on 307 patients following subsequent therapy. After a median follow up of 52.4 months, median OS for patients on Isa-Pd vs Pd was 24.6 vs 17.7 months (P=0.02). Additional treatment was administered to 66.2% patients who had received Isa-Pd vs 77.8% of Pd patients (daratumumab was used as part of subsequent therapy in 22.5% and 59.7% of patients, respectively). The ORR included:
- 28.8% Isa-Pd vs 35.5% Pd for first subsequent line of therapy
- 25% Isa-Pd vs 40.5% Pd for daratumumab-based regimen as first subsequent line of therapy
- 12.5% Isa-Pd vs 36.7% Pd for daratumumab monotherapy or steroids in any subsequent line of therapy
- 28.6% Isa-Pd vs 44.8 Pd for daratumumab in combination with IMiDs, alkylating agents, or PIs in any subsequent line of therapy
The PFS on first subsequent line of therapy that included daratumumab was 2.2 months for Isa-Pd vs 5.7 months for Pd and for first subsequent line of therapy excluding daratumumab was 4.6 vs 5.2 months. Subsequent anti-CD38 antibody was less effective in patients who had previously received Isa-Pd.
Results from the IKEMA trial (isatuximab-carfilzomib-dex [isa-Kd] vs carfilzomib-dex [Kd]) showed that significant PFS improvements were seen in RRMM patients (those who had received 1-3 prior lines of therapy) treated with the triplet regimen. Investigators evaluated the IKEMA data according to patients who experienced an early relapse (<12 months from initiation of most recent line of therapy [for patients who had ≥2 lines of therapy]; <18 months [for patients who had 1 prior line of therapy] and <12 months from ASCT) versus late (≥12 months from initiation of most recent line of therapy [for patients who had ≥2 lines of therapy (≥18 months [for patients who had 1 prior line of therapy]) relapse. Early relapse patients (n=107) in the isa-Kd arm had a higher frequency of renal impairment (31% vs 15.4%) and lower incidence of ISS Stage I (31.1% vs 54.3%) compared with patients in Kd arm (n=176). Late relapsed patients in the isa-Kd arm had a higher frequency of 1q21+ than patients in the Kd arm. Median PFS was longer for patients in the isa-KD arm vs Kd in both early (24.7 vs. 17.2months) and late (42.7 vs 21.9 months) relapse. ORRs were equivalent in early (82% vs 82.6%) and late (90.4% vs 86.1%) relapsed patients treated in either arm. However, more patients on the isa-Kd arm achieved at least a VGPR, MRD negativity, and MRD-negative CR rates than did patients in the Kd arm:
- ≥VGPR rate: early relapse, 67.2% vs 52.2%; late relapse, 76% vs 58.3%
- MRD negativity rate: early relapse, 24.6% vs 15.2%; late relapse, 37.5% vs 16.7%
- MRD-negative CR rate: early relapse, 18% vs 10.9%; late relapse, 30.8% vs 13.9%
Grade ≥3 and serious treatment-emergent adverse events (AEs) were similar in both treatment arms for early relapse patients but higher for late relapse patients in the isa-Kd arm. Regardless of early or late relapse, RRMM patients benefit from the use of isa-Kd with respect to depth of response and prolonged PFS.
Bispecific antibodies are another option for stimulating a patient’s T cells, and the first drug in this class, teclistamab, was approved earlier this year. Comprising two antigen-recognition domains designed to recognize CD3 expressed on T cells and a myeloma cell surface antigen, bispecific antibodies recruit T cells to myeloma cells and cause T-cell proliferation and myeloma cell lysis. Importantly, large quantities of bispecific antibodies can be generated and stored, which creates an off-the-shelf product—an advantage in clinical utility over CAR T-cell therapy. Several updates on bispecific antibodies were presented at ASH this year.
Teclistamab efficacy and safety in combination with daratumumab and lenalidomide in patients with RRMM (with only 1 to 3 prior lines of therapy) was investigated in the phase 1b multicohort MajesTEC-2 study. Patients (N=32; median 2 prior lines of therapy; 31.3% anti-CD38 exposed) received teclistamab-daratumumab-lenalidomide (tec-dara-len). Teclistamab was administered at a dose of 0.72 or 1.5 mg/kg with step-up dosing. The most frequent AE was CRS (81.3%, all grade 1/2). No ICANS was reported. Other AEs were neutropenia (75%; 68.8% G3/4), fatigue (43.8%, 6.3% G3/4), diarrhea (37.5%), insomnia (31.3%, 3.1% G3/4), cough (28.1%), hypophosphatemia (25%), and pyrexia (25%, 6.3 G3/4). Common infections included upper respiratory infection (21.9%), COVID-19 (21.9%), and pneumonia (21.9%). All evaluable patients receiving the 0.72 teclistamab dose responded to treatment (n=13); 13 of 16 receiving the 1.5 dose responded. The MajesTEC-7, phase 3 trial is under way to compare tec-dara-len with dara-len-dex as initial treatment for patients with newly diagnosed MM ineligible for ASCT.
Elranatamab is another BCMA-targeted bispecific antibody under investigation. In results from the phase 1 MagnetisMM-1 study of RRMM patients (N=55; 27% of patients were Black; median number of prior regimens was 5; 91% were triple-class refractory) given a ≥215 μg/kg dose of elranatamab, common AEs included CRS, neutropenia, anemia, injection-site reaction, and lymphopenia. Premedication and a single priming dose showed 67% of patients experiencing CRS (mainly grade 1 and 2; no grade 3 or higher). The ORR was 64%, with 56% of patients achieving ≥VGPR and 38% ≥CR. Among patients who had received prior BCMA-targeted therapy (n=13) of either antibody drug conjugate, CAR T-cell therapy, or both, 54% achieved a response (46% ≥VPGR). Twelve-month event-free survival was 59%, and median duration of response was 17.1 months. All patients (n=12) with confirmed ≥CR achieved MRD negativity (1 × 10-5 sensitivity). Durable clinical and molecular responses were seen with elranatamab; results from additional clinical trials are pending.
Results from the open-label nonrandomized phase 2 MagnetisMM-3 study investigating elranatamab in patients with RRMM (refractory to at least 1 PI, 1 IMiD, and 1 anti-CD38 antibody) were presented. Elranatamab 76 mg/week (with a two-step-up priming dose in the first week: 12 mg and 32 mg) was administered to 123 patients who had no prior BCMA-targeted treatment (7% were Black; 25.2% had high-risk cytogenetics; 15.4% had R-ISS III, and 31/7% had extramedullary disease; median 5 prior lines of therapy; 96.7% triple-class refractory). At a median follow-up of 6.8 months, 51.2% of patients were still receiving treatment. ORR was 61% with a clinical benefit observed for subgroups. Median duration of response has not been reached, and the probability of maintaining response at 6 months was 90.4%. Infections were reported in 61.8% of patients (grade 3/4 in 31.7%), namely upper respiratory tract infections (14.6%; no grade 3/4) and pneumonia (10.6%; 5.7% grade 3/4). Peripheral neuropathy developed in 17.1% of patients (0.8% grade 3/4)—47.6% of these patients had a history of neuropathy. In patients receiving the two-step-up dosing (n=119), CRS was reported in 56.3% and ICANS in 3.4% (all grade 1 and 2); approximately half of these patients received tocilizumab and/or steroids.
Alnuctamab is another BCMA-targeted bispecific antibody. Data were reported on both IV and SC formulations in 70 and 47 RRMM patients, respectively. Results showed:
- Patients receiving IV formulation:
- Median duration of response 146.1 weeks
- Evaluable patients receiving SC formulation:
- 51% ORR (all patients with evaluable samples achieved MRD negativity (1 × 10-5)
- Overall safety
- Most common AE was CRS (53%, all G1/2)
- Neutropenia (34%/30% G3/4)
- Anemia (34%/17% G3/4)
- Only 1 patient with ICANS
The phase 1/2 MonumenTAL-1 study was conducted to determine efficacy and safety of talquetamab, a G protein–coupled receptor family C group 5 member D (GPRC5D) × CD3 bispecific antibody in patients with RRMM. Results were presented for two randomized phase 2 doses (RP2Ds): 0.405 mg/kg SC weekly (QW) and 0.8 mg/kg SC every other week (Q2W). Patients with no prior exposure to T-cell redirecting therapies received talquetamab at the RP2Ds, with 143 patients treated at the 0.405 mg/kg QW dose and 145 patients at the 0.8 mg/kg dose Q2W. Baseline characteristics were similar between dosing groups: a median of 5 prior lines of therapy and the majority of patients triple-class exposed/refractory or penta-drug exposed/refractory. Results for each dosing group included:
- 0.405 mg/kg QW: 74% ORR; 59% ≥VGPR; 34% ≥CR with median time to response was 1.2 months, median duration of response was 9.3 months, and median PFS was 7.5 months
- Common AEs: CRS (79%), dysgeusia (48%), anemia (45%)
- Skin-related AEs and nail disorders occurred in 56% and 52% of patients, respectively
- 34% neutropenia and 27% thrombocytopenia (limited to first few cycles)
- 0.8 mg/kg Q2W: 73% ORR; 57% ≥VGPR; 32% ≥CR with median time to response was 1.3 months, median duration of response was 13 months, and median PFS was 11.9 months
- Common AEs: CRS (72%), dysgeusia (46%), anemia (39%)
- Skin-related AEs and nail disorders occurred in 68% and 43% of patients, respectively
- 28% neutropenia and 27% thrombocytopenia (limited to first few cycles)
This study showed promising efficacy and manageable safety in heavily pretreated myeloma patients; studies are ongoing.
Another GPRC5D bispecific antibody, RG6234, is being investigated in a phase 1 study in patients with RRMM. Administration of RG6234 was initiated with step-up dosing as both IV and SC formulations in 51 patients and 54 patients, respectively. Most patients were triple-class refractory (63%-73%), some had prior BCMA-targeted treatment (19%-20%); high-risk cytogenetics, such as t4;14, t(14;16), and del(17p) were common (46%-50%). Results showed:
- AE profile
- CRS was the most common AE (77.8%–82.4% of patients; ≥G3 1.9%–2%)
- ICANS-like AEs were infrequent (8.6%, ≥G3 1.9%)
- Dermal and epidermal AEs (72.5%–81.5%, G3 11.8%–14.8%)
- Hair and nail changes (17.6%–22.2%)
- Gastrointestinal mucosal epithelium or tongue (70.6%–74.1%, G3 5.6% G3)
- Infections (37%–56.9%, ≥G3 19.6%–24.1%)
- ORR in the IV and SC groups: 71.4% and 60.4%
- Responses in 55.6% of patients who had received prior BCMA-targeted therapy
- Reponses in 64.2% of patients with high-risk cytogenetics
Cevostamab is an FcRH5 targeted bispecific antibody under investigation in patients with RRMM. In an ongoing phase 1 study, investigators looked to add pretreatment with the anti–IL-6 antibody tocilizumab prior to the first dose of cevostamab to potentially reduce the incidence of CRS. A single 8 mg/kg dose of tocilizumab was administered to 28 patients 2 hours prior to cevostamab. Patients that did not receive tocilizumab (N=44) served as a comparator. Overall, 35.7% of patients receiving tocilizumab pretreatment experienced CRS compared to 90.9% of patients who didn’t. Grade 3 CRS was observed in only one patient in each group and no G4/5. The only difference in safety between arms was the frequency of neutropenia, which was higher for patients receiving tocilizumab (64.3% vs 38.6% G3/4). No impact on response was observed with tocilizumab pretreatment.
New Drugs on the Horizon: Next-Generation CAR T and Novel Mechanisms
Data from a phase 1 dose-escalation study of a GPRC5D-targeted CAR T-cell therapy, BMS-986393, was reported. Patients with RRMM (N=17) received different doses of a single infusion of 25, 75, or 150 × 106 CAR T cells. High-risk cytogenetics (del[17p], t[4;14], and/or t[14;16]) were present in 47% of patients, 47% had extramedullary disease, 41% receive prior BCMA-targeted therapy (35% prior CAR T), and 24% had penta-refractory disease. Results showed:
- Grade 3/4 AEs in 65% of patients; most frequent were neutropenia (41%) and thrombocytopenia (35%)
- Additional AEs include skin- (18%) and nail- related (12%); dysgeusia/dysphagia (12%); CRS (65%); ICANS (12%)
- 12 out of 14 evaluable patients responded (86%), including 7 of 11 patients treated with prior BCMA-targeted treatment
BMS-986354 is a next-generation CAR T-cell therapy that targets BCMA (the same construct as orvacabtagene autoleucel) and has a shortened manufacturing time through the NEXT-T process. Phase 1 results were presented on the use of BMS-986354 in patients with RRMM. Patients (N=55) were treated with a single infusion of BMS-986354 following lymphodepletion therapy (42 patients in the dose-escalation cohort and an additional 13 patients added to the dose-expansion cohort of 40 × 106 CAR T cells). Patients had received a median of 5 prior lines of treatment. CRS occurred in 80% of patients with only 1 patient experiencing ≥G3. Neurotoxicity occurred in 10.9% of patients (one grade 4). ORR was 98.1% with 57.4% achieving ≥VGPR (29.6% ≥CR). A more rapid processing time is anticipated!
A dual-targeting CAR T cell is under investigation in a phase 1 study as first-line therapy for newly diagnosed MM high-risk patients ineligible for stem cell transplant. GC012F is a BCMA/CD19 dual-targeting CAR T cell that can be produced via next-day manufacturing. The trial enrolled newly diagnosed patients with high-risk features such as R-ISS-2 or -3, del17p, t(4;14), t(14;16), or 1q21amp ≥4 copies, extramedullary disease, IgD or IgE subtype, LDH >upper limit of normal, or any of the high-risk definition of mSMART3.0. GC012F was administered to 13 patients as a single infusion at three dose levels following cyclophosphamide-fludarabine conditioning. After a median follow up of 5.3 months, 100% of patients achieved ≥VGPR (69% sCR) and all patients achieved MRD negativity (by EuroFlow). CRS was observed in 23% of patients (all low grade).
Modakafusp alfa is an immune-targeting cytokine consisting of two attenuated IFNα2b molecules fused to the Fc portion of an anti-CD38 IgG4 monoclonal antibody. Final safety and efficacy data of the phase 1/2 study was presented. Patients (N=100) were treated with modakafusp (56 in a dose escalation and 44 in expansion cohorts). Among the patients treated at the 1.5 mg/kg every 4 weeks dose (n=30), the ORR was 43% and median duration of response was not reached. Median PFS was 5.7 months. Grade 3 or higher AEs were reported in 87% of patients.
Another novel cereblon E3 ligase modulator (CELMoD) is mezigdomide (CC-92480), which exhibits enhanced tumoricidal and immune-stimulatory effects compared to IMiDs. Results from the dose-expansion cohort of an ongoing phase 1/2 trial evaluating mezigdomide in combination with dexamethasone in patients with RRMM were presented. Patients (N=101) received mezigdomide + dex at the RP2D of 1 mg once a day. R-ISS stage III was seen in 20% of patients, 38.6% had plasmacytomas, and 36 of the 101 had high-risk cytogenetics (455 were not evaluable). The median number of prior lines of therapy was 6, which included ASCT (77.2%) and BCMA-targeted therapy (29.7%). All patients were refractory to lenalidomide and were triple-class refractory. ORR was 39.6% (2% sCR; 3% CR, 17.8% VGPR, 16.8% PR); 30.8% in patients with plasmacytomas and 50% in patients with prior BCMA-targeted therapy. At a median follow up of 5.8 months, the median duration of response was 8.3 months and median PFS was 4.6 months. The most frequent grade 3/4 AEs were neutropenia (74.3%), anemia (32.7%), and thrombocytopenia (25.7%). Phase 3 trials in combination with PIs are planned.
Support for this activity has been provided through donations from Amgen and Karyopharm; grants from Bristol Myers Squibb and Genentech, a member of the Roche Group; and sponsorships from AbbVie, GSK, and Sanofi US.
For patient educational resources from our sponsors, be sure to click on the following links: