Paul G. Richardson, MD

Paul G Richardson, MD, clinical program leader and director for Clinical Research, Jerome Lipper Multiple Myeloma Center, institute physician at Dana-Farber Cancer Institute, and RJ Corman professor of Medicine at Harvard Medical School, discusses the ways treatment approaches for patients with multiple myeloma has changed over the past few years.

The multiple myeloma space has seen various FDA-approvals come through, including belantamab mafodotin (Blenrep), melphalan flufenamide (Melflufen), as well as chimeric antigen receptor (CAR) T-cell agents like idecabtagene vicleucel (ide-cel; Abecma), and ciltacabtagene autoleucel (cilta-cel; Carvykti).

With the addition of new agents underway, Richardson hopes that further understanding of these exciting treatment updates in multiple myeloma from a research standpoint can improve patient outcomes in real-world practices.

 I do want to emphasize that we've got multiple new agents in the pipeline. One of the features of my presentation is around the exciting new class of drugs, called the CELMoD which are extremely powerful oral agents. That's an important practical point to share, that we're looking for real world options for our patients as well. Exciting platforms like CAR T are important, but they require hospitalization. Bispecifics are perhaps less complicated in terms of their modality, but nonetheless, they still require hospitalization, at least initially.

 When you put this all together, having the availability of oral options that we can take off the shelf in the absolute sense of the word, and deliver them to our patients in the outpatient setting, particularly in the context of the pandemic, is absolutely vital. I think that there's a lot of excitement coming with these new agents that are that much more convenient to use, and practical, as well as recognizing in myeloma anyway, that our patients, unfortunately, are uniquely vulnerable to COVID-19. For that reason, practical approaches that don't increase vulnerability to COVID-19, in every sense, are particularly important.

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Paul G Richardson, MD, discusses the ways treatment approaches for patients with multiple myeloma has changed over the past few years.

Emerging Treatment Options in the Multiple Myeloma Space

Paul G. Richardson, MD, clinical program leader and director for Clinical Research, Jerome Lipper Multiple Myeloma Center, institute physician at Dana-Farber Cancer Institute, and RJ Corman professor of Medicine at Harvard Medical School, discusses the latest regulatory movement in the multiple myeloma space, a topic he touched on during a presentation at the 3rd Summit of the Americas on Immunotherapies for Hematologic Malignancies.

According to Richardson, a large number of FDA approvals came through just before the COVID-19 pandemic. The approvals begin with belantamab mafodotin (Blenrep), Melphalan flufenamide (Melflufen), and chimeric antigen receptor T-cell therapies including idecabtagene vicleucel (ide-cel; Abecma), and ciltacabtagene autoleucel (cilta-cel; Carvykti).

In the near future, Richardson and other who treat multiple myeloma are anticipating FDA action for a bispecific antibody.

 Over the last several years we've seen a number of drugs approved, we start really just before the pandemic or just around the pandemic with belantumab mafadotin. And at the same time, we then had Melflufen approved. And then subsequent to that, and most recently, we had in addition to ide-cel’s approval, which was critical, which is the first CAR T platform, then the second CAR T platform, which was cilta-cel approved, which is extremely exciting.

 Plus multiple approvals around certain indications like for example, selinexor combined with bortezomib in the early relapse setting and other further indications for either isatuximab as a CD38-targeting antibody, and additional indications for CD38-targeting with daratumumab in different settings as well. So, I think there are multiple approvals, but probably the highlights would be the successes in the CAR T space, in particular either ide-cel and then very excitingly, and very recently cilta-cel.

 In the terms of belantumab mafadotin which targets BCMA as antibody-drug conjugate, that was some years ago now, but continuing to gain momentum. And then we did have the impressive approval of now Melflufen, a targeted peptide drug conjugate, although that's currently gone into a holding pattern pending some interpretation of important phase 3 data from a trial that showed different benefits in different subgroups of patients, which caught the regulator's attention appropriately and has generated some discourse and discussion about how to best go forward with that particular platform.

Irrespective of that, we've got incredible work coming from bispecifics. These are antibodies that harness the immune system from within as it were, by basically targeting BCMA but at the same time harnessing a DT cell response dramatically to the target. And the bispecifics space I think is probably in the next to see an exciting new approval hopefully this year.

Paul G. Richardson, MD, discusses the latest regulatory movement in the multiple myeloma space.

Newly-Approved Therapies and Pending Applications in Myeloma

Paul G. Richardson, MD, clinical program leader and director of Clinical Research for the Jerome Lipper Multiple Myeloma Center at Dana-Farber Cancer Institute, and RJ Corman Professor of Medicine at Harvard Medical School, discusses the response rates observed in the first-in-human phase 1 trial (NCT03374085) of CC-92480 and dexamethasone in patients with relapsed/refractory multiple myeloma.

Richardson said the overall response rate (ORR) for all of the evaluable patients in the study was about 21%, and the ORR for the patients treated at the maximum tolerated dose was encouraging at 40%, including 2 patients with complete response. When Richardson and the investigators looked at the best schedule, the response rate was at about 55% for the recommended phase 2 dose.

The majority of patients, about 70%, who were receiving the combination at 1 mg for 3 weeks and then were off for 1 week, were triple-class refractory and achieved complete responses and very good partial responses, which was exciting, according to Richardson.

For patients who had extramedullary disease and were receiving 1 mg, there were observed responses reflected by paraproteins and the disappearance of extramedullary disease on scans, which was something the investigators did not expect, Richardson says. All of the responses were durable in the study.

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Paul G. Richardson, MD, discusses the response rates observed in the first-in-human phase 1 trial of CC-92480 and dexamethasone in patients with relapsed/refractory multiple myeloma.

Evaluating Response Rates With CC-92480 Combination in Multiple Myeloma

Paul G. Richardson, MD, clinical program leader and director of clinical research of the Jerome Lipper Multiple Myeloma Center, Dana Farber Cancer Institute and RJ Corman Professor of Medicine, Harvard School of Medicine, discusses the interesting safety and efficacy profiles of the HORIZON trial.

The phase II, multicenter study looked at the combination of melflufen and Dexamethasone (Ozurdex) in patients with relapsed/refractory multiple myeloma who were refractory to pomalidomide (Pomalyst), daratumumab (Darzalex), or both.

The safety profiles showed that most toxicities were grades 1 and 2. Expected adverse events like suppression of blood counts, hair loss, mucositis, and peripheral neuropathy were either manageable or did not occur.

Paul G. Richardson, MD, clinical program leader and director of clinical research of the Jerome Lipper Multiple Myeloma Center, Dana-Farber Cancer Institute and RJ Corman Professor of Medicine, Harvard School of Medicine, discusses the interesting safety and efficacy profiles of the HORIZON trial.

Melflufen Plus Dexamethasone Safe and Effective For R/R Multiple Myeloma

Paul G. Richardson, MD, clinical program leader and director of Clinical Research in the Jerome Lipper Multiple Myeloma Center at Dana-Farber Cancer Institute, discusses results from the phase III OPTIMISMM trial comparing treatment regimens for relapsed/refractory multiple myeloma. This data compares a regimen of pomalidomide (Pomalyst), bortezomib (Velcade), and dexamethasone versus bortezomib and dexamethasone alone.

The results for the 3-drug regimen over the 2-drug regimen were quite striking, Richardson says. The first thing they noted as significant was the progression-free survival. For patients who had progressed or relapsed after 1 prior line of therapy, there was significant clinical benefit over 10 months.

The hazard ratio in the experimental arm was 0.5, which Richardson says was also very meaningful. The response rate overall was 82% in the experimental arm versus around 60% in the control arm.

Paul G. Richardson, MD, clinical program leader and director of Clinical Research in the Jerome Lipper Multiple Myeloma Center at Dana-Farber Cancer Institute, discusses results from the phase III OPTIMISMM trial comparing treatment regimens for relapsed/refractory multiple myeloma. This data compares a regimen of pomalidomide, bortezomib, and dexamethasone versus bortezomib and dexamethasone alone.&nbsp;

Paul G. Richardson, MD | Authors

Articles

Emerging Treatment Options in the Multiple Myeloma Space

Newly-Approved Therapies and Pending Applications in Myeloma

Evaluating Response Rates With CC-92480 Combination in Multiple Myeloma

Melflufen Plus Dexamethasone Safe and Effective For R/R Multiple Myeloma

Comparing Results for 3-Drug and 2-Drug Regimens in Relapsed/Refractory Myeloma