ASH Annual Meeting and Exposition

ASH Annual Meeting and Exposition

Perspective from Noopur Raje, MD
Perspective from Paul G. Richardson, MD
December 07, 2015
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Despite advances in triplets, HSCT continues to confer benefit in multiple myeloma

Perspective from Noopur Raje, MD
Perspective from Paul G. Richardson, MD
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ORLANDO, Fla. — Autologous hematopoietic stem cell transplantation should remain a standard of care for younger patients with de novo multiple myeloma, according to phase 3 study results presented at the ASH Annual Meeting and Exposition.

Further, treatment with lenalidomide (Revlimid, Celgene), bortezomib (Velcade; Millennium Pharmaceuticals, Takeda Oncology) and dexamethasone plus autologous hematopoietic stem cell transplantation (HSCT), may act as a future reference strategy, according to the researchers.

“The rate of survival after 4 years remains high in both study arms,” Michel Attal, MD, professor at University of Toulouse in France, said during a presentation. “However, transplantation is already associated with a reduced risk for death due to myeloma. Thus, in the era of new drugs, transplantation should remain a standard of care.”

High-dose chemotherapy, followed by autologous HSCT, currently serves as the standard of care for newly diagnosed younger patients (≤ 65 years) with multiple myeloma. However, the high complete response rate associated with triplet combinations of immunomodulatory drugs, proteasome inhibitors and dexamethasone have led investigators to propose this strategy as an upfront treatment without immediate transplantation, according to study background.

Thus, Attal and colleagues sought to determine whether autologous HSCT was still required for the initial management of younger patients with multiple myeloma.

The researchers conducted a randomized trial comparing conventional-dose treatment, or RVD, to RVD plus autologous HSCT in 700 previously untreated French and Belgian patients (median age, 58 years).

Patients on the RVD arm received eight cycles of lenalidomide, bortezomib and dexamethasone, plus stem cell mobilization after three cycles using high-dose chemotherapy and granulate-colony–stimulating factor. Patients on the transplant arm received three induction cycles of RVD, underwent stem cell collection and HSCT conditioned with melphalan (Alkeran, GlaxoSmithKline), and then received two consolidation cycles of RVD.

Patients in both arms received lenalidomide maintenance (10-15 mg per day) for 1 year. Patients in the RVD arm could undergo HSCT at time of relapse.

PFS served as the primary endpoint.

Median follow-up was 41 months.

At time of reporting, all patients had discontinued treatment (completion of therapy = 66%; disease progression = 16%; adverse events = 10%).

In the transplant arm, 93% of patients underwent HSCT, with five toxic deaths occurring during mobilization or in the actual transplant phase.

HSCT appeared associated with improved PFS (4-year PFS, 47% vs. 35%; P <.001).

The transplant group’s PFS benefit extended across all subgroups, including subgroups based on age, sex, immunoglobulin isotype, International Staging System stage, cytogenetics and response after first three cycles.

Significantly more patients in the transplant arm achieved a complete response (59% vs. 49%; P < .01). However, the high 3-year post-randomization OS rate (88%) remained similar between study groups.

Attal and colleagues further observed a correlation between transplantation and an increased rate of minimal residual disease negativity (80% vs. 65%; P < .001) and improved time to progression (49% vs. 35%; P < .001).

The researchers recorded 41 second primary malignancies in 39 patients (transplant, n = 23; RVD, n = 18).

A parallel U.S. trial using a similar design remains ongoing, according to Attal.

“The design of this trial is absolutely similar to the trial in France, except for the duration in maintenance,” Attal said. “Maintenance therapy was 1 year in the French trial and will be until progression in the U.S. trial. The results of the U.S. trial remain crucial.” – by Cameron Kelsall

Reference:

Attal M, et al. Abstract 391. Presented at: ASH Annual Meeting and Exposition; Dec. 5-8, 2015; Orlando, Fla.

Disclosure: Attal reports honoraria from Janssen and an advisory board position with Celgene. Please see the abstract for a list of all other researchers’ relevant financial disclosures.