– Optimal induction therapy for patients with multiple myeloma requires all the therapeutic tools currently available for combination therapy, which means using four agents followed by autologous stem cell transplantation, Paul G. Richardson, MD, said at a conference held by Imedex.

He suggested that a rational combination regimen for induction therapy of multiple myeloma would include a second- or third-generation immunomodulator such as lenalidomide (Revlimid) or pomalidomide (Pomalyst); a proteasome inhibitor such as bortezomib (Velcade), carfilzomib (Kyprolis), or ixazomib (Ninlaro); plus standard dexamethasone to form a contemporary backbone regimen for inducing remission in patients with multiple myeloma.

Mitchel L. Zoler/Frontline Medical News

Dr. Paul G. Richardson (left) and Dr. Ruben Niesvizky

Dr. Richardson advocated for the addition of an anti-CD38 monoclonal antibody such as daratumumab (Darzalex), as well as follow-up management with an autologous stem cell transplant, a total package of treatments that has not yet been tested in a reported trial.

“Therapeutic parsimony is not recommended. You need a combination” of all available drug classes, suggested Dr. Richardson, professor of medicine at Harvard Medical School and clinical program leader of the Multiple Myeloma Center at the Dana-Farber Cancer Institute in Boston.

“It isn’t rational to limit the treatment choices. We need to bring them all together,” he said. The “most rational” combination melds an immunomodulator, proteasome inhibitor, plus a monoclonal antibody that he called a “true game changer. Add the antibody on top of the three-drug platform” of an immunomodulator, proteasome inhibitor, and dexamethasone. Dr. Richardson conceded, however, that a concern with such combinations is how to manage the toxicity that would likely result.

He cited several recent examples of demonstrated superior efficacy in the form of more complete responses from combined regimens, followed by autologous stem cell transplantation.

For example, a recent report from a French-led group compared the efficacy of a combination of an immunomodulator, proteasome inhibitor, and dexamethasone against the same combination, followed by autologous stem cell transplantation (N Engl J Med. 2017 Apr 6;376[14]:1311-20). The combined regimen plus transplant resulted in a 59% complete response rate, “the best response rate we’ve ever seen” in multiple myeloma, Dr. Richardson noted, compared with a 48% complete response rate in patients who did not undergo a stem cell transplant.

Another speaker at the meeting, Ruben Niesvizky, MD, suggested a more cautious approach to using the monoclonal antibody daratumumab for induction. He cited the published experience in adding the antibody to pared-down backbone therapy in the setting of relapsed or relapsed and refractory disease, such as a proteasome inhibitor plus dexamethasone (N Engl J Med. 2016 Aug 25;375[8]:754-66) or an immunomodulator plus dexamethasone (N Engl J Med. 2016 Oct 6;375[14]:1319-31).

Adding a monoclonal antibody such as daratumumab to combination therapy is the “wave of the future,” said Dr. Niesvizky, professor of medicine and director of the Multiple Myeloma Center at New York Presbyterian Hospital/Weill Cornell Medical Center. It provides treatment that reduces disease-related complications and achieves effective and extended disease control with improved overall survival, while being well tolerated and facilitating stem cell collection.

Dr. Richardson has been a consultant to Celgene, Genmab, Janssen, Novartis, Oncopeptides AB, and Takeda and has received research funding from Celgene and Takeda. Dr. Niesvizky has been a consultant to Amgen, Bristol-Myers Squibb, Celgene, Janssen, and Takeda and has received research support from Amgen, Bristol-Myers Squibb, Celgene, and Takeda.

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