Less May Be More in Treating High-Risk Myeloma
FROM THE ANNUAL MEETING OF THE AMERICAN SOCIETY OF HEMATOLOGY
Major Finding: Patients with high-risk cytogenetics treated with intensive therapy had a median overall survival of 46 months vs. 71 months if treated with nonintensive therapy (P = .01).
Data Source: Retrospective analysis of 208 patients with multiple myeloma.
Disclosures: Dr. Baz reported research funding from Celgene and membership on an entity’s board of directors or advisory committee and research funding from Millennium Pharmaceuticals. His coauthors reported similar relationships with Celgene, Millennium, Novartis, and Allergan. Dr. Lacy reports research funding from Celgene.
SAN DIEGO – A provocative analysis suggests that a sequence of bortezomib and lenalidomide provides a better survival advantage than regimens with three or more agents in patients with multiple myeloma and high-risk cytogenetics.*
"While the limitations of this retrospective study limit drawing definitive conclusions, it appears that poor cytogenetics and biology trump treatment intensification," Dr. Rachid Baz and his colleagues stated in a poster presentation at the annual meeting of the American Society of Hematology.
The investigators reported on 208 patients with multiple myeloma who received bortezomib (Velcade) and lenalidomide (Revlimid), nonconcurrently between January 2004 and August 2010 at the H. Lee Moffitt Cancer Center and Research Institute in Tampa. The patients were stratified by treatment into six groups: lenalidomide with or without dexamethasone (lenalidomide A) or lenalidomide in combination with two or more agents (lenalidomide B); bortezomib with or with dexamethasone (bortezomib A) or bortezomib in combination with two or more agents (bortezomib B); and finally, only doublets or single agents (nonintensive therapy) or three or more agents in combination (intensive therapy).
No differences were observed between the lenalidomide A and B, bortezomib A and B, or intensive and nonintensive therapy groups in the baseline characteristics of age, International Staging System (ISS) and Durie/Salmon stage, beta2microglobulin or renal function, presence of poor-risk cytogenetics, and frequency of high-dose therapy.
Poor-risk cytogenetics, an increasingly fluid term in the context of growing success with novel myeloma agents, included deletions 13q and 17p, translocations, (4;14) and (14;16) or hypodiploidy.
Lenalidomide A patients had a trend toward improved median overall survival at 72 months, compared with 57 months for the lenalidomide B group receiving more complex regimens (P = .07), reported Dr. Baz, with Moffitt’s hematologic malignancies and experimental therapeutics departments.
Median overall survival, the study’s primary end point, however, was significantly improved in the bortezomib A group at 72 months vs. 45 months in the bortezomib B group (P = .02).
Similarly, the nonintensive therapy group lived significantly longer for 74 months vs. 57 months for the intensive therapy group (P = .03).
Notably, patients with high-risk cytogenetics had significantly worse survival if they received intensive therapy rather than nonintensive therapy (median 44 months vs. 72 months; P = .01), he noted. In contrast, patients without high-risk cytogenetics had similar overall survival regardless of whether they belonged to the intensive therapy or nonintensive therapy groups (median 76 months vs. 75 months).
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Begin With the End Point in Mind
"This is an intriguing observation," Dr. Martha Q. Lacy said in a separate interview. "The author points out that it is a retrospective study, and results could be confounded by a number of variables, so I agree that one cannot take this as the definitive word on this subject. This should be studied in well-designed prospective studies. It also underscores the need to design trials with overall survival as the primary end point.
"Increasingly, myeloma studies have used remission rates and progression-free survival as primary end points," she said. "If studies are not designed with overall survival as the end point, we risk missing potentially critical insights into the best treatment strategies."
Dr. Lacy is with the hematology division at the Mayo Clinic in Rochester, Minn.