Earlier this month, the FDA approved isatuximab-irfc (Sarclisa®, Sanofi), an anti-CD38 monoclonal antibody, in combination with pomalidomide and dexamethasone for adults with multiple myeloma who have received at least two prior lines of treatment, including lenalidomide and a proteasome inhibitor. In this interview with i3 Health, Paul G. Richardson, MD, who served as the co-primary investigator of the ICARIA-MM study, on which the isatuximab approval was based, shares his thoughts on the significance of the approval, the adverse event profile for this regimen, and the progress that is being made in the treatment of relapsed/refractory multiple myeloma.
What are the greatest challenges of treating patients with relapsed/refractory multiple myeloma?
Paul G. Richardson, MD: Our greatest challenge is to be able to have combinations that can overcome resistance to other classes of drugs while having a manageable side effect profile in a way that can allow patients to receive continuous therapy and enjoy sustained benefit. In this regard, the isatuximab platform is very promising in my view. Also, an important point to share is that there are now numerous options available to patients that we can use sequentially to improve outcomes, and isatuximab-based therapy is a valuable addition to the armamentarium.
Can you comment on the significance of the FDA's approval of isatuximab in combination with pomalidomide and dexamethasone for the treatment of multiple myeloma in the third line and beyond?
Dr. Richardson: I think it's an important advance, as I outlined. In my opinion, it provides an excellent new treatment option for our patients, particularly in the more advanced setting, and the speed with which approval has been achieved is incredibly helpful for our patients, especially at this time of a global health emergency.
How does isatuximab/pomalidomide/dexamethasone compare with other options for the later-line treatment of multiple myeloma, in terms of both efficacy and adverse events?
Dr. Richardson: The combination, both in my experience and as reflected in the data overall, is well tolerated, and it's effective, critically after multiple lines of prior therapy have failed our patients. It is particularly attractive for patients with comorbidities such as chronic obstructive pulmonary disease and preexisting asthma because of the unique nature of the antibody. It also has a convenient schedule, with infusion reactions being rare, and at the same time, other side effects, such as low blood counts and upper respiratory infections, are generally manageable.
What additional treatment advances are on the horizon?
Dr. Richardson: There are numerous developments on the horizon, including combinations with isatuximab that include other three-drug regimens. We're very hopeful that these combinations will have greater efficacy and further improve outcomes more broadly.
Finally, what advice could you offer to community hematologists and oncologists treating patients with relapsed/refractory multiple myeloma?
Dr. Richardson: As the therapeutic horizon continues to expand favorably and as our treatment options remain excitingly dynamic with ongoing developments, especially in immunotherapy as well as with other novel approaches, I strongly feel that the outlook for our patients continues to improve. This approval represents one such major milestone on that journey.
About Dr. Richardson
Paul G. Richardson, MD, a hematologist-oncologist, is the Clinical Program Leader and Director of Clinical Research of the Jerome Lipper Multiple Myeloma Center at the Dana-Farber Cancer Institute, and he is the RJ Corman Professor of Medicine at Harvard Medical School. Dr. Richardson has led or co-led the study and clinical development of numerous drugs in the treatment of multiple myeloma, including thalidomide, lenalidomide, bortezomib, ixazomib, panobinostat, pomalidomide, elotuzumab, daratumumab, selinexor, and isatuximab, in addition to the study of the now-established lenalidomide/bortezomib/dexamethasone (RVD) combination approach, a new standard first-line therapy for multiple myeloma. He has also recently investigated the timing and evolving role of autologous stem cell transplant in multiple myeloma. Outside of his work in multiple myeloma, Dr. Richardson spearheaded the testing of the novel oligonucleotide defibrotide for the treatment and prevention of hepatic veno-occlusive disease complicating stem cell transplant in children and adults, from first concept in 1996 through to the approval-finding phase 3 trial in 2016, with further studies ongoing in endothelial cell injury from a diverse array of causes. He has been the recipient of the Warren Alpert Prize from Harvard Medical School, the Accelerator Award from the Multiple Myeloma Research Foundation, the Ernest Beutler Prize and Lecture from the American Society of Hematology, the COMy Award, and the Robert Kyle Award from the International Myeloma Foundation.
For More Information
Attal M, Richardson PG, Rajkumar SV, et al (2019). Isatuximab plus pomalidomide and low-dose dexamethasone versus pomalidomide and low-dose dexamethasone in patients with relapsed and refractory multiple myeloma (ICARIA-MM): a randomised, multicentre, open-label, phase 3 study. Lancet, 394(10214):2096-2107. DOI:10.1016/S0140-6736(19)32556-5
Clinicaltrials.gov (2020). Multinational clinical study comparing isatuximab, pomalidomide, and dexamethasone to pomalidomide and dexamethasone in refractory or relapsed and refractory multiple myeloma patients (ICARIA-MM). NLM identifier: NCT02990338.
Transcript edited for clarity. Any views expressed above are the speaker's own and do not necessarily reflect those of i3 Health.