Daratumumab Maintenance Improves Survival and Depth of Response in Multiple Myeloma

April 2020 Vol 11, No 4

Categories:

Multiple Myeloma

Following induction therapy with daratumumab (DARA) plus cyclophosphamide, bortezomib, and dexamethasone (CyBorD), monthly daratumumab maintenance therapy given for a year continued to improve depth of response in a group of patients with newly diagnosed or relapsed multiple myeloma. These data come from an update of the single-arm phase 2 LYRA study, presented by Robert M. Rifkin, MD, and colleagues at the 2019 ASH Annual Meeting.

“These data indicate that DARA-CyBorD is a safe, effective multiple myeloma treatment, and that daratumumab maintenance increases depth of response and achieves durable remissions,” reported Dr Rifkin.

Importantly, the investigators noted, the increase in complete responses in these patients was associated with durable progression-free survival (PFS) and overall survival (OS).

Daratumumab is currently approved for the treatment of newly diagnosed and relapsed/refractory multiple myeloma when used in combination with standard-of-care regimens. CyBorD is a commonly used immunomodulatory drug-sparing regimen recommended by the National Comprehensive Cancer Network as induction therapy for patients with multiple myeloma who are transplant eligible or ineligible.

LYRA is an ongoing open-label trial conducted at US community oncology centers; it is designed specifically for patients with newly diagnosed or relapsed myeloma that is not refractory to a proteasome inhibitor (PI) or PI/ immunomodulatory drug combination.

Patients in the study received a median of 6 and 8 cycles, respectively, of induction therapy with DARA and CyBorD. Dr Rifkin pointed out that the first dose of daratumumab was given over 2 consecutive days with hopes of decreasing the length of the infusion and the incidence and severity of infusion reactions.

After induction, all patients received up to 12 monthly maintenance cycles with IV daratumumab 16 mg/kg every 4 weeks, and eligible patients could undergo autologous stem cell transplantation (ASCT). Patients were followed for 36 months from the start of induction.

Dr Rifkin noted that high-risk cytogenetics were imbalanced between arms and were more common in newly diagnosed patients. “This was just the luck of the draw in a protocol that accrued very rapidly,” he said. “The preponderance of accrual was very rapid in the newly diagnosed arm, and with the first amendment of the protocol we actually closed the relapsed arm.”

In total, 101 patients with a median age of 63 years were enrolled in the study; 87 patients were newly diagnosed (1 had never received treatment), and 14 were relapsed. At the time of reporting, 39 newly diagnosed patients and 1 relapsed patient had undergone ASCT; 76 patients in the newly diagnosed group and 12 in the relapsed group had completed induction. Eighty-five patients received 1 or more maintenance doses of daratumumab, whereas 70 patients received all 12 maintenance cycles.

At the end of induction, the overall response rate (ORR) in newly diagnosed patients who did not receive a transplant was 83%, with 64% showing very good partial responses or better (≥VGPRs) and 11% demonstrating complete responses or better (≥CRs). But response rates in the newly diagnosed cohort deepened with 12 months of daratumumab monotherapy maintenance, particularly in patients who received a transplant.

By the end of maintenance, ORR, ≥VGPR, and ≥CR rates were 97%, 82%, and 49%, respectively, in newly diagnosed patients who underwent ASCT, and 83%, 70%, and 30%, respectively, in newly diagnosed patients who did not undergo transplant.

Induction with DARA-CyBorD followed by daratumumab maintenance also achieved high 2-year PFS rates in newly diagnosed patients—regardless of their transplant status—and depth of response was correlated with longer PFS in all newly diagnosed patients. After a median follow-up of almost 26 months, the 24-month PFS rate was 89% in transplant patients and 72.6% in nontransplant patients. OS data are immature, but “promising,” he added.

Even the limited number of patients in the relapsed population achieved a durable depth of response with daratumumab maintenance. Their rates of ≥CRs deepened over time, and 2-year PFS was 47.6%.

The safety profile in LYRA was consistent with previous reports of daratumumab, and no new safety concerns were observed with longer follow-up. Serious treatment- related adverse events occurred in approximately one-third of patients, with the most common (>2%) being pneumonia, pulmonary embolism, and atrial fibrillation, Dr Rifkin reported.

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Last modified: February 17, 2021

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