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July 27, 2020
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Three-drug induction regimen leads to high response rates after transplantation in myeloma

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Induction therapy with lenalidomide, bortezomib and dexamethasone demonstrated high response rates after transplantation among 90% of a cohort of patients with myeloma, according to study results published in Journal of Clinical Oncology.

Risk-adapted maintenance therapy also can lead to unprecedented long-term outcomes, researchers noted.

Induction therapy with lenalidomide, bortezomib and dexamethasone demonstrated high response rates after transplantation among a cohort of patients with myeloma.

This cohort represents the largest to date with long follow-up of patients treated with lenalidomide (Revlimid, Celgene), bortezomib (Velcade, Millennium/Takeda) and dexamethasone, a regimen known as RVD, according to the researchers. It also demonstrates the ability of triplet induction regimens to confer substantial survival benefits for this patient population.

“There have been signicant therapeutic advances in myeloma over the past few decades, leading to an improved survival benet for patients during this period,” Nisha S. Joseph, MD, assistant professor in the department of hematology and medical oncology at Emory University School of Medicine, and colleagues wrote. “The availability of novel classes of drugs, namely immunomodulatory drugs and proteasome inhibitors, and the increased use of autologous stem cell transplantation (ASCT) and continuous maintenance therapy have contributed to these sustained responses. Improvements in pre- and post-ASCT outcomes have been a result of the evolution toward the use of carefully crafted combination therapy required for newly diagnosed myeloma.”

Previous studies have shown that RVD is an effective and convenient induction regimen for both transplant-eligible and -ineligible patients with myeloma.

Joseph and colleagues analyzed 1,000 consecutive patients (median age, 61 years; range, 16-83; 54.6% male) with newly diagnosed myeloma treated with RVD induction therapy followed by risk-adapted maintenance therapy between January 2007 and August 2016 to determine responses and progression.

Researchers obtained clinical and demographic characteristics and outcomes data from the Emory University institutional review board-approved myeloma database.

Results showed an overall response rate of 97.1% after induction therapy and 98.5% following transplantation, with 89.9% of patients achieving a very good partial response or better and 33.3% achieving stringent complete response after median follow-up of 67 months.

Researchers reported median PFS of 65 months (95% CI, 58.7-71.3) for the entire cohort, 40.3 months (95% CI, 33.5-47) for patients with high cytogenetic risk status and 76.5 months (95% CI, 66.9-86.2) for patients with standard risk status.

Median OS for the entire cohort was 126.6 months (95% CI, 113.3-139.8), 78.2 months (95% CI, 62.2-94.2) for patients with high risk and not reached for patients with standard risk. Five- and 10-year OS rates were 57% and 29% for patients with high risk and 81% and 58% for patients with standard risk.

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The study’s retrospective nature served as a limitation.

“Our expectation is that ... prospective trials will eventually mature with longer follow-up and may show similar results to ours,” Joseph and colleagues wrote. “In the interim, our analysis, in addition to the currently available literature, provides a strong rationale for adopting multidrug combination strategies in the upfront treatment of patients with myeloma and makes a strong case for risk-adapted maintenance.”