At the 66th American Society of Hematology (ASH) Annual Meeting, Robert Rifkin, MD, FACP, hematologist oncologist at Rocky Mountain Cancer Center in Denver, Colorado, sat down for an interview with Pharmacy Times® to discuss multiple abstracts he worked on featuring drugs in the clinical trial process for patients with relapsed or refractory multiple myeloma (R/R MM).
Rifkin emphasizes the key role that pharmacists play in determining the correct treatment for patients with R/R MM, and notes strategies that pharmacists could employ to offer more optimized treatment to these patients, including creating a medically integrated pharmacy.
Pharmacy Times: What are the key points of the DREAMM-7 study that pharmacists and treatment providers should know about?
Key Takeaways
1. Belantamab Mafodotin: A Promising but Complex Drug: Belantamab mafodotin, a BCMA-targeted antibody-drug conjugate, demonstrated significant efficacy in treating multiple myeloma. However, its use was limited by severe ocular toxicity, leading to its withdrawal from the US market. Future research may focus on mitigating these side effects to unlock its full potential.
2. In-Class Transition to Oral Therapy: Improved Patient Experience: The MM-6 trial highlighted the benefits of transitioning patients to an oral regimen (ixazomib-lenalidomide-dexamethasone) after initial induction therapy. This approach improved patient quality of life by reducing treatment burden and increasing adherence, especially during the pandemic.
3. Potential for Long-Term Oral Maintenance Therapy: The long-term safety and efficacy data from the MM-6 trial suggest that oral regimens may play a valuable role in maintaining disease control in patients with multiple myeloma. Further studies are needed to explore the optimal duration and timing of these therapies.
Robert Rifkin: The entire DREAMM program is interesting because it focused on a drug that we'll just call belan-maf (belantamab mafodotin) right now, because that's very long name. It's an antibody-drug conjugate that has a BCMA target for treating myeloma. BCMA, or B-cell maturation antigen, is present in 98% of multiple myeloma patients. It was a new target, and the target's only approachable right now with CAR T-cells or bispecific antibodies. This was a drug that was completely different as an antibody drug conjugate.
Pharmacy Times: What are the potential clinical implications of this finding for patients with multiple myeloma, particularly in terms of quality of life and long-term disease control?
Rifkin: As you know, the belan-maf molecule was pulled from the United States market, and then recently, in New England Journal of Medicine papers, DREAMM-7 and DREAMM-8 were published and met the survival end points. So that was very exciting. However, with it goes an off-target effect, if you will, which is the ocular toxicity or corneal injury. That was really the thing that made it difficult to use the drug and kind of tarnish the reputation of a very, very active drug.
Pharmacy Times: Can you discuss the unique mechanism of action of belantamab mafodotin and how it contributes to its efficacy in multiple myeloma?
Rifkin: It's an antibody drug conjugate. There are a lot of those in other hematologic diseases, but it's unique because it seeks out the BCMA target and then kills the cells with the warhead, if you will, on the molecule. So that's unique. We've used it in other diseases, but again, it was really the first drug in multiple myeloma that worked that way; unfortunately, it came with its unique set of toxicities.
Pharmacy Times: Regarding your analysis of US MM-6 in abstract 4757, could you discuss the long-term safety profile of this regimen, particularly in patients with multiple comorbidities?
Rifkin: MM-6 is a trial that we started several years ago. The hypothesis behind it was that you could give any bortezomib (Velcade; Millenium Pharmaceuticals)-based induction, and after 3 cycles, patients are then eligible to switch over to an all-oral regimen, which is ixazomib-lenalidomide-dexamethasone (IRd). Initially, accrual was very slow, but interestingly, the pandemic intervened, and nobody wanted to come to doctor's offices. So, a once a month, all oral regimen was very, very exciting. With that, it took off. The pandemic passed; we're still following patients, because initially they were allowed 3 full years of the IRD regimen, and some have remained on way longer than that, and it was very, very active, very easy to give with minimal toxicity. Where it may even play a role going forward is not the in-class transition I outlined, but maybe for somebody with a slow relapse of myeloma, where you don't have to take out all the big guns that we just talked about, but an all-oral regimen works very well in that setting as well. We're excited to present updated data at this meeting.
Pharmacy Times: What are the impacts of in-class transition to oral therapy on patient quality of life, particularly in terms of treatment burden, adherence, and overall patient experience?
Rifkin: This is interesting because of the whole study evolving during the pandemic, but what we found is, after you get in a few cycles, and maybe a tweak is made here or there, that it's very easy to administer, very well-tolerated. Patients enjoyed a really good quality of life while they're on IRD.
The 66th ASH Annual Meeting and Exposition takes place from Saturday, December 7 to Tuesday, December 10 in San Diego, California. You can follow our continuing coverage here.
Pharmacy Times: How can pharmacists provide adequate treatment counseling to patients with multiple myeloma given the variety of treatments that have shown efficacy in this population?
Rifkin: I think pharmacists can play a key role. One approach is a medically integrated pharmacy where, for example, I would write you a prescription for ixazomib (Ninlaro; Takeda Pharmaceuticals); you would fill it, or whoever the payer would let fill it, would do that. With that in our system would come a call with the pharmacist, in addition to the education that we would do in the clinic, reinforcing things and providing a readily available contact. The pharmacists are very important in the medically integrated pharmacy.
