Promising Results Seen with the Addition of Daratumumab to Standard of Care in Myeloma Patients Eligible for Transplant

Adding the drug daratumumab to a standard treatment combination containing lenalidomide, bortezomib, and dexamethasone (called RVd for short) led to fast and long-lasting responses in patients with newly diagnosed multiple myeloma who were well-suited for autologous stem-cell transplantation (ASCT). ASCT is an important treatment in patients with newly diagnosed multiple myeloma, but not all patients are a good fit for it.

Importantly, the length of a patient’s responses actually increased the longer they were treated with the 4-drug combo. Response to cancer treatment is one way to tell how effective a treatment is, and responses are divided into categories like “complete” and “partial,” depending on how well a patient did after treatment.

Research has shown that stringent complete response and minimal residual disease (MRD)-negativity after ASCT are associated with better survival. Stringent complete response is the highest classification of treatment response, and is better than complete response, very good partial response, partial response, or stable disease. MRD is a term used to describe the small number of cancer cells in the body after cancer treatment, so an  MRD-negative  result means that no disease was detected after treatment. Doctors use MRD to measure the effectiveness of treatment and to predict which patients are at risk of relapse.

These exciting results come from an update of the phase 2 GRIFFIN clinical trial. Clinical trials are designed to test the safety and effectiveness of new drugs. Phase 2 trials like GRIFFIN are carried out with a fairly small number of patients, and tell doctors more about how safe a cancer treatment is and how well it works.

Investigators on the GRIFFIN trial studied the safety and effectiveness of adding daratumumab to RVd and ASCT. The study included 207 newly diagnosed transplant-eligible patients, and they were assigned to receive either RVd and ASCT alone or RVd and ASCT in addition to daratumumab.

“The study met its primary end point, with daratumumab and RVd improving the stringent complete response rate by the end of consolidation therapy,” said Peter Voorhees, MD, one of the study’s lead investigators. Consolidation therapy is used to kill any cancer cells that may be left in the body after initial treatment, and comes before maintenance therapy (all patients in the study received 24 months of maintenance with RVd with or without daratumumab).

With longer follow-up, responses deepened over time in all patients, whether or not they received daratumumab, but patients in the daratumumab arm continued to perform better. Response rates and depths were greater in the daratumumab group at all time points in the trial, including end of induction (the first part of treatment), end of ASCT, and end of consolidation.

When the researchers collected these data, the rates of complete response or better were close to 80% in the daratumumab/RVd group, compared with 61% in the RVd arm. A complete response means that a patient had no evidence of myeloma cells in their bone marrow or blood. Stringent complete response rates were 62.6% with daratumumab versus 45.4% without.

MRD-negative rates were 51.0% with daratumumab versus 20.4% without daratumumab. Importantly, 47.1% of patients who were given daratumumab achieved both MRD-negativity and a complete response, compared with only 18.4% in the other group.

“If we just look at patients who achieved complete response, a higher proportion of patients in the daratumumab arm were MRD-negative, suggesting that the quality of complete responses was better in the daratumumab arm,” said Dr. Voorhees.

The addition of daratumumab also seems to be improving progression-free survival and overall survival in these patients. Progression-free survival is the length of time that a person lives with their cancer without it getting any worse. Overall survival is the length of time from the start of treatment that patients diagnosed with their cancer are still alive.

“Looking at initial progression-free and overall survival rates, suffice it to say that both groups of patients are doing incredibly well,” said Dr. Voorhees.

At 2 years, progression-free survival is 95.8% in the daratumumab arm versus 89.8% in the RVd arm, and overall survival is 95.8% versus 93.4%.

The side effects of treatment were manageable, but there was more serious neutropenia and thrombocytopenia in patients who received daratumumab. Pneumonia and serious infections occurred at a similar rate in the 2 groups, but patients who received daratumumab had higher rates of mild upper respiratory tract infections. There were no treatment-related deaths.

“These data demonstrate that adding daratumumab to RVd significantly improves response rates and depth of response, including continued improvement of stringent complete response and MRD-negativity rates beyond post-ASCT consolidation,” Dr. Voorhees added. “As seen in other randomized studies, continued use of daratumumab improved the depth of response.”

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