ASH 2015: Trials exploring new settings for monoclonal antibodies in MM

by Thomas R. Collins: Trials are continuing to explore potential new settings for daratumumab and elotuzumab, two monoclonal antibodies that were recently approved for use in multiple myeloma (MM) in the U.S. New data was presented here at the 57^th Annual Meeting of the American Society of Haematology.

Daratumumab, which targets CD38, was approved in November in the U.S. for use as a single agent after at least 3 prior lines of therapy, including a proteasome inhibitor (PI) and an immuodulatory agent, or for patients who are double-refractory to a PI and an immodulatory agent.

Elotuzumab, which targets CS1, was also approved in November in the U.S., for use with lenalidomide and dexamethasone in patients who have failed 1 to 3 prior lines of therapy.

Daratumumab and elotuzumab have been granted accelerated review status in Europe.

Both CS1 and CD38 are highly expressed in MM — both of the antigens are seen in about 90% of cases. Both therapies work both through direct anti-tumor effects and through immunomodulation.

In two trials, daratumumab is being tried as part of a combination therapy — in one Phase 2 with lenalidomide and dexamethasone (Rd) and in another, a Phase 1b trial, with pomalidomide and dexamethasone. ^1,2

At a median follow-up of about 18 months, 34% of the dara-len-dex patients achieved a complete response or better. At a follow-up of about 4 months, 9% of patients in the dara-pom-dex trial had a CR or better.

No new safety signals emerged in either study, investigators said, as both were similar to the safety profile seen with either len-dex or pom-dex alone.

Randomized Phase 3 studies of dara-len-dex are ongoing in relapsed/refractory and newly diagnosed MM patients, said Torben Plesner, MD, Professor of Hematology at the University of Southern Denmark.

In another trial, elotuzumab plus the PI bortezomib and dexamethasone was compared to bortezomib and dexamethasone in relapsed/refractory MM patients.

Investigators found that the median progression-free survival for the elotuzumab group was 9.7 months, compared to 6.9 months in the other group — a 28% reduction in the risk of disease progression or death.

The safety profile for the elotuzumab-bortezomib-dexamethasone regimen was similar to that of the bortezomib and dexamethasone combination.

Antonio Palumbo, MD, Chief of the Myeloma Unit in the Department of Oncology at the University of Torino in Italy, and the principal investigator on the trial, said elotuzumab in combination with bortezomib and dexamethasone shows, so far, roughly the same benefit as elotuzumab-lenalidomide-dexamethasone, although he acknowledged that fewer patients have been studied with the bortezomib combination. ³

“This is a plus for a clinician because it certainly gives us the opportunity to use bortezomib or lenalidomide according to previous exposures to those drugs,” he said. “On the other hand, lenalidomide with continuous treatment might have an advantage over bortezomib, while bortezomib might have an advantage in terms of a more rapid, decisive reduction.”

References

1. Plesner T, Arkenau H, Gimsing P, et al. Daratumumab in combination with lenalidomide and dexamethasone in patients with relapsed or relapsed and refractory multiple myeloma: Updated results of a phase 1/2 study (GEN503). Presented at the 57th Annual Meeting of the American Society of Hematology. 2015 Dec 5-8. Orlando FL. Abstract 507.
2. Chari A, Lonial S, Suvannasankha A, et al: Open-label multicenter phase 1b study of daratumumab in combination with pomalidomide and dexamethasone in patients with at least 2 lines of prior therapy and relapsed or relapsed and refractory multiple myeloma. Presented at the 57th Annual Meeting of the American Society of Hematology. 2015 Dec 5-8. Orlando FL. Abstract 508.
3. Palumbo A, Offidani M, Pegourie B, et al. Elotuzumab Plus Bortezomib and Dexamethasone Versus Bortezomib and Dexamethasone in Patients with Relapsed/Refractory Multiple Myeloma: 2-Year Follow-up. Presented at the 57th Annual Meeting of the American Society of Hematology. 2015 Dec 5-8. Orlando FL. Abstract 510.