If this works out a lot of us may live longer

Post in Research


Key clinical point: The investigational anti-CD38 antibodies SAR650984 and daratumumab in combination with standard regimens were highly active in untreated and relapsed/refractory multiple myeloma.

Major finding: Overall response rates were 58% in patients treated with SAR650984, and 100% and 50%, respectively, in newly diagnosed and relapsed patients given daratumumab. Data source: Two phase Ib studies in patients with newly diagnosed or relapsed/refractory multiple myeloma.

Disclosures: Sanofi Oncology sponsored the SAR650984 study. Dr. Martin reported research funding from Sanofi and serving as a speaker for Novartis. Genmab sponsored the daratumumab study. Dr. Mateos and Dr. Moreau reported ties with Janssen. Dr. Kahl reported ties with numerous drug companies.

SAN FRANCISCO – Combining anti-CD38 monoclonal antibodies with standard antimyeloma therapies proved highly active without excessive toxicity in newly diagnosed as well as relapsed or refractory multiple myeloma in a pair of phase Ib studies.

“These anti-CD38 antibodies are the next blockbuster class of agents,” Dr. Thomas Martin III, lead author of one of the studies, said during a press briefing at the annual meeting of the American Society of Hematology. “These are the next agents that are really going to show some benefit for myeloma patients. And the next 5 years are going to be really fun moving them from the refractory setting to the less refractory setting to the frontline setting.”

Three agents are in development that target CD38, a cell surface glycoprotein that is strongly expressed in multiple myeloma. All three – daratumumab, SAR650984, and MOR202 – bind to a different part of the anti-CD39 receptor, but “whether that makes any clinical difference, we certainly don’t know at this point in time,” said Dr. Martin of the University of California, San Francisco.

Immunomodulatory drugs (IMiDs) and proteasome inhibitors (PI) are the current blockbuster agents in myeloma and have advanced overall survival from about 3 years to 7-10 years. But all patients still relapse after IMiD and PI failure, and survival outcomes remain poor at a median of about 9 months for those with advanced relapsed/refractory disease. Further, myeloma has failed to respond like the B-cell lymphomas to anti-CD20 antibodies such as rituximab (Rituxan).

Dr. Martin and his associates launched a phase Ib dose-escalation trial to evaluate SAR650984 in combination with standard doses of lenalidomide (Revlimid) and dexamethasone in adults with relapsed or refractory multiple myeloma failing at least two prior therapies.
SAR650984 was given intravenously on days 1 and 15 of a 28-day cycle at 3 mg/kg to 4 patients (cohort 1), 5 mg/kg to 3 patients (cohort 2), and 10 mg/kg to 6 patients (cohort 3) plus an additional 18 patients in an expansion cohort.

All 31 patients were heavily pretreated, with 94% previously treated with lenalidomide or bortezomib (Velcade), 29% with pomalidomide (Pomalyst), and 48% with carfilzomib (Kyprolis). Many (84%) were considered double refractory, or relapsed and refractory, to their last IMiD therapy, Dr. Martin reported…

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This group of immunotherapy agents  is our/my best hope for a significantly extended life.  Along with ARRY-520 (a completely different class of drug) some of us may be able to stretch things out until an even more effective group of therapies are developed.

We may end of glowing in the dark and become translucent in daylight, hobbling along, connected to IV tubes, with artificial hips replacing joints ravaged by years of dexamethasone use–but we’ll still be alive, dammit!

Believe it or not, works for me, as long as the next generation of patients coming up behind me are granted a better quality of life.  And the new biologics hold out the hope of far fewer side effects, a welcome respite from the subtle pounding we take cycle after cycle of this drug combination and that.