Combination daratumumab, bortezomib, and dexamethasone therapy (DVd) at first relapse was well-tolerated and produced high response rates in patients with relapsed/refractory multiple myeloma. Researchers presented their findings at the 63rd ASH Annual Meeting & Exposition.

“Discrepancies in outcomes between patients treated in clinical trials compared to routine practice [are] well recognized due to a combination of patient, disease, and treatment-related factors,” authors wrote, adding that clinical practice typically involves weekly administration of bortezomib, as opposed to the biweekly administration used in the previous phase 3 CASTOR study. “As a result, the real-world outcomes of patients treated with DVd are yet to be determined.”

The authors conducted a retrospective analysis that spanned 14 health care facilities and included 288 patients, of median 69 years of age, who were treated with DVd between March 2019 and June 2021.

“Patients received daratumumab ([intravenous] and then [subcutaneous] from June 2020) weekly in cycles 1-3, on day 1 of a 3-week cycle during cycles 4-8, and then monthly from cycle 9 to progression,” researchers wrote. “[Subcutaneous] bortezomib was predominantly given weekly for cycles 1-8,” or biweekly for patients with more aggressive forms of the disease.

Most patients (93%) had received 1 prior line of treatment, and 18 patients (7%) had received 2 prior therapies. Authors noted that this patient sample differed from that of the CASTOR study in several ways, including older age, more exposure to bortezomib (71% vs 51%, P=.0003), and higher criterion for glomerular filtration rates (<30 mL/min vs <20 mL/min).

The overall response rate for patients receiving DVd was 76%, with 54% of patients achieving very good partial response or better. Median time to response was 1.6 months.

After 15 months of follow up, authors reported that the median progression-free survival (PFS) for all patients in the sample was 14 months (95% CI 11.6-16).

Patients with high cytogenetic risk had a median PFS of 10 months (95% CI 6-14), while median PFS was not reached in patients with standard risk (P=.043). Median PFS was also not reached among patients with stage I disease, but patients with stage II and stage III disease had a median PFS of 15 months and 12 months, respectively (P=.05).

Authors also noted that median PFS was:

• 3 months for patients with extramedullary disease (95% CI 1-5);
• 10 months for patients who were proteasome inhibitor (PI)-refractory vs 15 months for PI-sensitive patients (P=.006); and
• not significantly different among patients with prior PI exposure vs no prior PI exposure (15 vs 13 months; P=.75).

Treatment lasted a median of 8 months, and the median time to next treatment was 21 months (95% CI 17-25).

Median overall survival has not been reached in the full sample, but data indicated 16-month overall survival for patients with high cytogenetic risk (95% CI 9-23; vs not reached for standard risk; P=.0006). Researchers estimated 2-year overall survival of 74% and 36% for all patients and for those with high cytogenetic risk, respectively.

After comparing weekly vs biweekly administration of bortezomib, authors reported no significant differences in response rate (83% vs 85%; P=.71), median PFS (11 vs 15 months; P=.14), or overall survival (not reached for either; P=.38).

“These real-world data of DVd at [first] relapse demonstrated good tolerability and high response rates with a weekly bortezomib schedule despite a more heterogenous population,” researchers concluded. “However, high risk patients…had inferior outcomes as did those treated within 12 months from first-line treatment.”

Reference:
McMillan A, Basu S, Karunanithi K, et al. Daratumumab, bortezomib and dexamethasone (DVd) at first relapse for patients with relapsed/refractory multiple myeloma (RRMM): a UK Myeloma Research Alliance (UK-MRA) real-world multicentre analysis. Poster presented at: 63rd ASH Annual Meeting & Exposition; December 11-14, 2021: Atlanta, GA.