Expert Point of View: Philip ­McCarthy, MD

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This may be another step forward utilizing very effective treatment for high-risk multiple myeloma to prevent end-organ damage and control the disease long term.
— Philip ­McCarthy, MD

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The ASCO Post asked Philip ­McCarthy, MD, Professor of Oncology and Internal Medicine at Roswell Park Cancer, Buffalo, and Director of the Blood and Marrow Transplant Center there, to comment on these study findings. He first addressed the need to study earlier intervention for smoldering myeloma.

“As Dr. Ghobrial has noted, we used to wait until a smoldering myeloma patient had end-organ dysfunction/damage before initiating therapy. Sometimes development of CRAB [hypercalcemia, renal insufficiency, anemia, bone lesions] criteria would be missed, as a patient would develop rapid renal failure or a skeletal fracture, both of which can have excessive morbidity,” stated Dr. McCarthy.

Building on Work by PETHEMA

According to Dr. McCarthy, the Ghobrial study builds upon the work of the Spanish PETHEMA group, particularly the trial by Mateos et al examining lenalidomide (Revlimid)/dexmethasone vs observation for smoldering myeloma.1 The enrollment criteria for the two studies were similar, although PETHEMA enrolled patients based on the Spanish criteria, whereas Ghobrial et al allowed patients who met either the Spanish or Mayo criteria. PETHEMA was randomized and had a longer follow-up (median of 40 months), he pointed out.

Since the follow-up time of the current study is short, noted Dr. McCarthy, “What we don’t know for sure is whether or not the addition of elotuzumab ­[Empliciti] to lenalidomide/dexamethasone will translate into an increased benefit. Also, this is a phase II study, so the comparisons will be indirect until a larger phase III study can be undertaken.”

Another Step Forward

Dr. McCarthy continued: “Of note, the responses were so good with lenalidomide/dexamethasone [79% overall, 11% very good partial response or better] that it will take a large number of patients and longer follow-up to definitively state that adding elotuzumab to lenalidomide/dexamethasone will improve outcomes. It will be very interesting to see detailed patient demographics from the Ghobrial study, so as to make an indirect comparison to the ­PETHEMA trial. It will also be important to look at correlative science studies, which would examine endpoints such as minimal residual disease and reversal of immune paresis.”

Caveats notwithstanding, Dr. ­McCarthy called the finding of tolerability with the addition of elotuzumab “very exciting.” Furthermore, he suggested, “This may be another step forward utilizing very effective treatment for high-risk multiple myeloma to prevent end-organ damage and control the disease long term.” ■

Disclosure: Dr. McCarthy received honoraria from Celgene, Bristol-Myers Squibb, Janssen, Karyopharm, and Takeda and research funding from Celgene.


1. Mateos MV, Hernandez MT, Giraldo P, et al: Lenalidomide plus dexamethasone for high-risk smoldering multiple myeloma. N Engl J Med 369:438-447, 2013.

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The high response rates among this patient population, who would otherwise remain untreated, is a promising starting point for the paradigm shift toward early therapeutic intervention in patients with high-risk smoldering myeloma.
— Irene Ghobrial, MD

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