This is our last day in the beautiful city of Vienna! And as we close out the IMW program, today we heard more presentations about treatments for newly diagnosed and relapsed/refractory patients.
Treatment for Newly Diagnosed Multiple Myeloma
High-Risk Multiple Myeloma
During the first full day of presentations at IMW (see our Day 1 blog here) we learned about some treatment strategies for patients with high-risk myeloma, that is, patients who have cytogenetic abnormalities that put them at a higher risk of relapse than patients who don’t have these abnormalities. Today, a presentation from clinicians at the Mayo Clinic reported on their analysis of a subset of patients with chromosome 1 abnormalities from the ENDURANCE trial. This was a head-to-head trial that compared the efficacy of Velcade-Revlimid-dex (VRd) and Kyprolis-Revlimid-dex (KRd) in over 1,000 patients with standard/intermediate-risk newly diagnosed myeloma who deferred an immediate ASCT. The investigators showed that, regardless of the treatment regimen used, patients with chromosome 1 abnormalities—specifically amplification of the long arm or deletion of the short arm—have inferior outcomes (such as shorter time to disease progression) than patients without these abnormalities. The investigators state that longer follow up and confirmatory studies are needed to draw any definitive conclusions.
MRD-Guided Therapy Duration
The reason the detection of minimal residual disease (MRD; which is the persistence of myeloma cells following a response to treatment) in myeloma patients is of interest to the myeloma community is that patients who achieve MRD negativity after treatment (that is, when no myeloma cells are detectable using specific tests) live longer than patients who remain MRD positive (that is, when myeloma cells are detectable). MRD testing in this way is used as a way to provide clinicians and patients with information about how well a patient may do after treatment. However, MRD testing is not yet used to help physicians decide whether to stop treatment or de-escalate therapy in patients who achieve MRD negativity. One trial led by Luciano Costa at the University of Alabama at Birmingham investigated whether MRD testing can help guide treatment decisions. In this study, 123 newly diagnosed myeloma patients (most of whom had high risk cytogenetic abnormalities) were treated with a 4-drug induction regimen (Darzalex-Kyprolis-Revlimid-dex) followed by an ASCT and then patients received 0, 4, or 8 cycles of the same quadruplet regimen as consolidation therapy after ASCT based on their MRD testing results. The results showed:
- 80% of patients achieved MRD negativity with treatment
- MRD negativity was reached in 38% of patients post induction therapy and 65% post ASCT and 80% post MRD-directed consolidation therapy
- Overall, 71% of patients have reached confirmed MRD negativity and are now being monitored—without treatment—for MRD resurgence 6 months after treatment was stopped and yearly thereafter
Ultimately, this study showed that patients who achieve a deep response (that is, MRD negativity) might be able to receive fewer cycles of treatment overall. We look forward to learning how the MRD-negative patients being observed fare!
For a quick video that visually explains all about MRD and how it is measured, please check out our High Impact Topic video here. You can also hear from two myeloma experts on the latest MRD updates here.
Treatment for Relapsed/Refractory Multiple Myeloma
Pepaxto (melflufen)
Pepaxto is a first-in-class drug called a peptide-drug conjugate. Pepaxto targets certain enzymes in the myeloma cell which releases chemotherapy (melphalan, the same drug most commonly used prior to a stem cell transplant) into the cell, killing it. Pepaxto is approved—in combination with dex—for treatment of patients with relapsed/refractory myeloma who have received at least four prior lines of therapy and whose disease is refractory to at least one proteasome inhibitor (such as Velcade, Kyprolis, or Ninlaro), one immunomodulatory agent (such as Revlimid or Pomalyst), and one CD38-directed monoclonal antibody (such as Darzalex or Sarclisa). To learn more about Pepaxto, click here.
Results from a phase 3 trial, called the OCEAN study, was presented today. What is important about this study is that it directly compared 2 doublet regimens, both of which are standards of care for patients with relapsed/refractory myeloma: (1) Pepaxto-dex and (2) Pomalyst-dex. Over 490 patients who were previously exposed to a median of 3 lines of therapy (almost all patients were refractory to Revlimid) were treated with either regimen. The main findings of this study included:
- Pepaxto-dex lengthened time to disease progression compared to Pomalyst-dex (6.8 months vs 4.9 months)—which was mainly driven by patients who had not received a prior ASCT
- Pomalyst-dex lengthened overall survival compared to Pepaxto-dex (25 months vs 19.8 months) particularly in patients who had a prior ASCT whereas Pepaxto-dex had a favorable survival rate in patients without a prior ASCT
- More patients experienced side effects such as low white blood cell, red blood cell, and platelet counts with Pepaxto-dex than with Pomalyst-dex which caused more patients to discontinue treatment with Pepaxto-dex than Pomalyst-dex
The investigators suggest that Pepaxto-dex can be used as a treatment option for patients with relapsed/refractory myeloma who are refractory to Revlimid and have had 2 to 4 prior lines of therapy and who have not received a prior ASCT. Further analysis of the data from this trial is ongoing. As of July, the FDA required that enrollment of patients on this trial and other trials with Pepaxto be suspended due to an increased risk of death in patients receiving this treatment. For patients already receiving Pepaxto, the FDA recommends patients discuss with their doctors the risks and benefits of receiving Pepaxto.
Patients Who Relapse from CAR T-Cell Therapy
The CAR T-cell therapy Abecma is now approved for patients with relapsed/refractory disease, and is very effective, but patients can relapse after this treatment. Clinicians from the Icahn School of Medicine at Mount Sinai evaluated the clinical outcomes of 31 myeloma patients (26 of whom had high-risk cytogenetics) who relapsed after CAR T therapy at their institution. Most of the patients had been highly pretreated with a median of 5 prior lines of therapy and 90% of patients had previously had a stem cell transplant. The majority of patients had been exposed to and were refractory to most myeloma agents such as: Revlimid, Velcade, Kyprolis, and Darzalex or Sarclisa. Some patients (13%) had previously received a non-BCMA-targeted bispecific antibody. The investigators showed:
- The median time to subsequent treatment following relapse on CAR T cell therapy was 34 days
- Most patients had 2 subsequent treatment lines and the most common was chemotherapy (V-DECP or VD-PACE)
- Twelve patients had a stem cell boost
- Five patients were treated with a bispecific antibody immediately following CAR T relapse while 11 patients received this treatment at any point after CAR T relapse
- 48% of patients responded to their initial treatment following CAR T relapse
- Median time to progression after initial treatment following CAR T relapse was 104 days and 62 days for second line after CAR T cells
- Durable responses (greater than 120 days) occurred with some treatments which were Xpovio-based, non-BCMA-targeted bispecific antibody-based, and stem cell boost-based, and venetoclax-based
Ultimately, the investigators concluded that there is “life after CAR T” which means that patients who relapse after CAR T cell therapy can receive and respond to other treatments that are available. Very encouraging information, indeed!
Be sure to hear what myeloma experts Dr. Faith Davies and Dr. Gareth Morgan have to say about the day’s presentations here. For all of our daily video interviews, please click here and here.
Thanks for following along with us at IMW this year!
