‘VCD-Lite’ Viable Option for Older, Toxicity-Vulnerable Myeloma Patients

Dose-attenuated bortezomib, cyclophosphamide, and dexamethasone (VCD-lite) is a viable treatment option for vulnerable or frail adults with newly diagnosed multiple myeloma, according to the results of a small study published in the Journal of Geriatric Oncology.

“With the high and increasing proportion of patients with multiple myeloma being very old and/or otherwise vulnerable to chemotherapy toxicity, it is increasingly important to determine the best regimens for treating these patients, yet existing clinical studies largely miss that mark by focusing on younger, fitter patients,” wrote Sascha A. Tuchman, of the University of North Carolina, Chapel Hill, and colleagues. “The best regimens maximize the likelihood of multiple myeloma control, ie, efficacy, while minimizing risk of severe toxicity. This is of particular importance in the vulnerable patient population under discussion, which is especially subject to severe sequelae of toxicity due to the loss of homeostatic reserve that arises with normal aging, compounded in many cases by specific medical comorbidities.”

According to the study, undergoing full-dose chemotherapy with VCD often leads to excessive toxicity in very old or frail adults with newly diagnosed multiple myeloma. With this study, Tuchman and colleagues wanted to test dose-attenuated VCD to see it this regimen would be better suited for these patients. VCD-lite consisted of subcutaneous bortezomib 1.3 mg/m², cyclophosphamide 300 mg/m², and dexamethasone 40 mg on days 1, 8, and 15 of a 28-day cycle for 8 cycles, followed by indefinite alternating bortezomib and lenalidomide maintenance. 

Fourteen patients were enrolled on the study, but it was closed early because of slow accrual.

“We encountered accrual challenges primarily due to many subjects’ clear preference for a more convenient induction, such as the all oral lenalidomide and dexamethasone combination,” the researchers wrote.

The intention-to-treat overall response rate was 64%, and the median progression-free survival was 24.2 months. The median overall survival was 29.7 months. The researchers called these outcomes promising, since 57% of the participants had high-risk genetics and 43% were International Staging System (ISS) stage III.

Sixty-four percent of patients experienced grade 3 or worse adverse events; 14% of patients discontinued treatment due to toxicity, 26% due to progression, and 29% due to other reasons.

The researchers also explored the use of the Cancer and Aging Research Group geriatric assessment as a predictor of toxicity. All patients except one completed the assessment. The researchers noted that non-hematologic severe toxicity was common and did not seem to correlate with geriatric assessment-derived predictions.

“Meanwhile, regarding current clinical practice we recognize recent studies that have shown that induction regimens that incorporate both proteasome inhibitors and immunomodulatory agents are likely the emerging standard of care for newly diagnosed myeloma,” the researchers wrote. “As a result, off protocol we frequently employ the dose-reduced lenalidomide, bortezomib, dexamethasone (‘RVD-lite’) for patients willing to come for once weekly bortezomib.”