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Transplant-Eligible Newly Diagnosed MM
Considerations for Transplant-Eligible Newly Diagnosed Multiple Myeloma

Released: May 02, 2024

Expiration: May 01, 2025

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Key Takeaways
  • For the management of transplant-eligible newly diagnosed multiple myeloma, we are seeing improvements in patient outcomes with the addition of an anti-CD38 monoclonal antibody to standard triplet therapy such as VRd or KRd.
  • With the shift to quadruple-drug regimens, there is an increased rate of hematologic toxicities.
  • Managing myelosuppression and the risk of infection will continue to be important for patients with newly diagnosed multiple myeloma.

In this commentary, Charise Gleason, MSN, NP-C, AOCNP, highlights the latest clinical findings on the use of quadruple-drug regimens for the management of transplant-eligible newly diagnosed (ND) multiple myeloma (MM). To find out more about the use of anti-CD38 monoclonal antibodies in clinical practice and the management of ND MM, visit the educational program “What’s New in Newly Diagnosed Multiple Myeloma: Current Concepts, Emerging Approaches."

Transplant-Eligible ND MM
For transplant-eligible ND MM, we recently saw results from 2 trials that highlighted the benefit of adding an anti-CD38 monoclonal antibody (daratumumab or isatuximab) to standard triplet regimens such bortezomib/lenalidomide/dexamethasone (VRd) or carfilzomib/lenalidomide dexamethasone (KRd).

The multicenter, open-label phase III PERSEUS trial compared daratumumab plus VRd (Dara-VRd) vs VRd in patients with transplant-eligible ND MM. Patients (N = 709) received upfront VRd with or without daratumumab followed by transplant and 2 cycles of consolidation with Dara-VRd or VRd. Patients on the VRd arm received single-agent lenalidomide maintenance, and patients on the Dara-VRd arm received daratumumab with lenalidomide maintenance. On the Dara-VRd arm, if patients were measurable residual disease (MRD) negative after 24 months, they continued single-agent lenalidomide maintenance. If patients were MRD positive, they continued with daratumumab plus lenalidomide as maintenance. The 4-year progression-free survival rate for Dara-VRd vs VRd was 84% vs 68%. This translated to a 58% reduction in the likelihood of disease progression (HR: 0.42; 95% CI: 0.30-0.59; P <.0001), and the benefit with Dara-VRd was consistent across subgroups, including cytogenetics risk, disease stage, and performance status. The safety profile for Dara-VRd was characterized by more hematologic toxicities vs VRd. The rate of grade 3-4 neutropenia was 62% vs 51%, and grade 3-4 thrombocytopenia was 29% vs 17%, respectively. Rates of anemia were similar at approximately 6% on each arm. Based on the results of the PERSEUS trial, Dara-VRd is now considered standard of care for transplant-eligible ND MM. 

In the open-label, randomized, phase III IsKia EMN 24 trial, 302 transplant-eligible patients with ND MM received induction therapy with isatuximab plus KRd (Isa-KRd) or KRd followed by autologous stem cell transplant. After transplant, patients received consolidation with Isa-KRd or KRd and then a light consolidation with lower doses of lenalidomide and dexamethasone. Results showed increased postconsolidation MRD negativity measured by next-generation sequencing with Isa-KRd vs KRd—77% vs 67% at the 10-5 cutoff (P = .049) and 67% vs 48% at the 10-6 cutoff (P <.001), respectively. MRD negativity improved with the addition of isatuximab in all subgroups, including high-risk and very high‒risk disease. As expected, the safety profile of Isa-KRd also was characterized by an increase in hematologic toxicities vs KRd. The rate of grade 3-4 neutropenia was statistically higher with Isa-KRd vs KRd (36% vs 22%; P = .008). Rates of grade 3-4 anemia (3% on both arms) and thrombocytopenia (15% vs 17%) were similar on both arms.

Managing Myelosuppression and Infection
With the shift to quadruple-drug regimens, myelosuppression can be more substantial than with triplet therapy. Most myeloma centers are aggressive with their antimyeloma treatment to improve overall patient outcomes, and instead of holding treatment, they may opt to use growth factor support (such as filgrastim for neutropenia) for myelosuppression. There are no recommended dose modifications for the anti-CD38 monoclonal antibodies. However, dose modifications may be considered for lenalidomide, proteasome inhibitors, and/or dexamethasone based on package insert instructions.

With myelosuppression, we also see an increased risk of infections, particularly with the addition of CD38 monoclonal antibodies. We typically prescribe herpesvirus prophylaxis, such as acyclovir, when starting patients on myeloma therapy—especially for those receiving a proteasome inhibitor or an anti-CD38 monoclonal antibody. For patients receiving a multidrug regimen with anti-CD38 monoclonal antibodies and high-dose corticosteroids, we prescribe Pneumocystis jirovecii pneumonia prophylaxis. We also advise patients to stay current on appropriate vaccines, including COVID-19 and annual influenza vaccines. Vaccine recommendations may vary from institution to institution, but in general, we follow the CDC guidelines.

Your Thoughts?
Are you routinely using quadruplets for the management of transplant-eligible ND MM? What do you find most challenging in your current clinical practice related to the care of patients with MM? Answer the polling question and leave a comment to join the discussion.

For more insights and updates across cancer types—including sessions on CD38-targeted therapies and bispecific antibodies in MM specifically designed for advanced practice providers—join us virtually on May 18 for APPlexus Hot Topics 2024.

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