Maria Chaudhry, MBBS, a hematologist at The Ohio State University Comprehensive Cancer Center—James, discusses novel treatment regimens in relapsed/refractory multiple myeloma.

One agent that is being used in the relapsed/refractory setting is daratumumab (Darzalex), says Chaudhry. Typically, daratumumab is used at the time of first relapse in combination with pomalidomide (Pomalyst) and dexamethasone.

In terms of other agents, carfilzomib (Kyprolis) is a very potent proteasome inhibitor that can be given in combination with pomalidomide and dexamethasone at the time of first and second relapse, adds Chaudhry. Generally, the most common treatment backbones in the relapsed/refractory setting are pomalidomide and dexamethasone.

In addition to daratumumab, another monoclonal antibody called isatuximab has shown activity in the relapsed/refractory setting. The agent was evaluated in combination with pomalidomide and dexamethasone in the phase III ICARIA-MM trial. Results showed that the triplet reduced the risk of progression or death by 40% versus pomalidomide and dexamethasone alone.

In July 2019, the FDA accepted a biologics license application for the triplet, which may lead to another option for patients with relapsed/refractory disease, concludes Chaudhry.

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Maria Chaudhry, MBBS, a hematologist at The Ohio State University Comprehensive Cancer Center&mdash;James, discusses novel treatment regimens in relapsed/refractory multiple myeloma.

Dr. Chaudhry on Novel Treatment Regimens in Relapsed/Refractory Multiple Myeloma

Maria Chaudhry, MBBS, a hematologist at The Ohio State University Comprehensive Cancer Center—James, discusses unmet needs in relapsed/refractory multiple myeloma.

The unmet need in multiple myeloma is largely with patients who have relapsed/refractory disease. This is because at second relapse and later, patients have difficult-to-control disease with toxicities that add up, explains Chaudhry. Patients who relapse within the next 2 years will have received bortezomib (Velcade) or carfilzomib (Kyprolis) as frontline therapy, which allows an anti-CD38 agent in the relapsed/refractory setting to still be relevant, says Chaudhry.

Additionally, data from the CANDOR trial looking at daratumumab (Darzalex), carfilzomib, and dexamethasone are promising and suggest a regimen free of immunomodulatory drugs. Chaudhry plans on using this regimen in her practice and anticipates daratumumab will be increasingly used in the frontline setting. When these patients relapse, they will require agents with different mechanisms of action, according to Chaudhry.

Clinical trials looking at different drugs in multiple myeloma continues, including studies evaluating monoclonal antibodies and bispecific T-cell engagers that target plasma cells. Chaudhry believes a few of these drugs may be FDA approved in 2020, providing this patient population with more options should they relapse.

Maria Chaudhry, MBBS, discusses unmet needs in relapsed/refractory multiple myeloma.

Dr. Chaudhry on Unmet Needs in Relapsed/Refractory Multiple Myeloma

Maria Chaudhry, MBBS, a hematologist at The Ohio State University Comprehensive Cancer Center—James, discusses the use of daratumumab (Darzalex), lenalidomide (Revlimid), and dexamethasone (DRd) in transplant-ineligible patients with multiple myeloma.

In the phase III MAIA trial, transplant-ineligible patients were randomized to receive DRd or the combination of lenalidomide and dexamethasone alone until progression. Approximately 44% of patients were 75 years of age or older.

The addition of daratumumab resulted in a 44% reduction in the risk of progression or death versus the combination alone, says Chaudhry. Moreover, the overall response rate (ORR) with daratumumab was also better, at 93%. Data from the trial served as the basis for the regimen’s approval in June 2019.

In terms of adverse events, the incidence of grade ≥3 neutropenia was higher in the daratumumab arm, concludes Chaudhry.

Maria Chaudhry, MBBS, discusses the use of daratumumab (Darzalex), lenalidomide (Revlimid), and dexamethasone in transplant-ineligible patients with multiple myeloma.

Maria Chaudhry, MBBS

Articles

Dr. Chaudhry on Novel Treatment Regimens in Relapsed/Refractory Multiple Myeloma

Dr. Chaudhry on Unmet Needs in Relapsed/Refractory Multiple Myeloma

Dr. Chaudhry on DRd Triplet in Transplant-Ineligible Multiple Myeloma