Earlier Daratumamab Use Feasible for Relapsed/ Refractory Multiple Myeloma

Adam D. Cohen, MD, Director, Myeloma Immunotherapy, Abramson Cancer Center of the University of Pennsylvania, Philadelphia, shares data from several studies that explored  the use of daratumamab earlier in multiple myeloma treatment.

Transcript

Hi. My name is Adam Cohen. I'm a hematologist-oncologist at the University of Pennsylvania at the Abramson Cancer Center where I focus on multiple myeloma and other plasma cell diseases.

Today, I'm going to talk about my takeaways from the 2018 American Society of Hematology meeting, which was held in San Diego. I think there were three broad themes that were exciting at ASH this year. I'll talk about several abstracts grouped into these three categories. The first was a group of abstracts that explored of use of daratumamab earlier in multiple myeloma treatment.

The daratumamab, the anti-CD38 antibody, has been approved as a single agent for heavily relapsed/refractory patients, was approved in combination with lenalidomide or bortezomib for patients with 1 to 3 prior lines of therapy, with pomalidomide in more heavily pretreated, and just recently in combination with bortezomib, melphalan, prednisone for newly diagnosed patients.

At this year's ASH, there were a few abstracts that looked at other daratumamab-based combinations again in less heavily pretreated patients. I think the most important of these is the late-breaking abstract presented by Falcon and colleagues of the MAIA trial. This was a randomized phase 3 for newly diagnosed myeloma patients who are ineligible for stem cell transplant, an older population.

The randomization was to either daratumamab, Revlimid, and dexamethasone versus Revlimid and dexamethasone. This was a trial that enrolled over 700 patients with a median age of 73. Patients were stratified based on their ISS stage, as well as their age. The primary endpoint was progression-free survival. Patients received either DRD or RD until progression.

The primary findings of the study were that there was a higher response rate in the DRD arm versus RD with 79% of patients choosing a VGPR or better with DRD compared to 53% for RD, and a complete remission rate of 48% with DRD versus 25% for RD.

I think importantly, the primary endpoint of progression-free survival was met. The median progression-free survival was 31.9 months for RD, and not reached for DRD with a hazard ratio of 0.55. The survival data was too immature. There was a trend towards improvement with the DRD on.

There was increased neutropenia and leukopenia, as well as some increased risk of pneumonia with the DRD arm. That's the trade-off here. Overall, this is a well-tolerated regimen with majority of patients being able to stay on study.

I think this is important because it likely will lead another approval for daratumamab for newly diagnosed patients. Along with the prior study with the Dara-VMP versus DMP really shows for this non-transplant eligible patient population. Adding dara does seem to improve both depth of response, as well as progression-free survival.

There were two additional abstracts looking at dara-based combinations for newly diagnosed patients. These were smaller studies. Dr. Shaji Kumar in Abstract 304 presented data on daratumamab, ixazomib, Revlimid, dex combination or Dara-IRD.

There were 38 patients treated in this phase 2 study. Most of which did not go to stem cell transplant, again demonstrating the feasibility and general well tolerability of this combination with an overall response rate of 98%, more than 69% getting VGPR or better.

Finally, Pete Voorhees, MD, presented in Abstract 151, preliminary data from the safety run-in from the Griffin randomized trial of dara, bortezomib, lenalidomide, dex, or Dara-VRD versus VRD in combination with stem cell transplant, followed by Dara-VRD or VRD consolidation, and then maintenance.

In this small experience of 16 patients, they again found that adding the dara upfront was feasible and generally well-tolerated. So far, again, promising response rate with 100% VGPR or better and 63% with CR or better.

I think, again, this just shows the feasibility of moving dara up earlier. I think we're going to see more of these dara-based triplets and quadruplets in newly diagnosed patients and may wait the results of further randomized phase 3 trials to see if this actually gets approved and becomes part of standard practice.

The last abstract I'll mention in this theme of earlier use of dara is Abstract 3271. This is the MM-014 trial, a multi-site, phase 2, single arm study of daratumamab, pomalidomide, and dex, or DPD, in lenalidomide exposed patients with 1 to 2 prior lines of therapy.

This was really trying to answer the question of what do we do with the patient who has had no response to initial therapy, gone on to lenalidomide maintenance, and then is progressing on len maintenance or progressing on a len-based therapy.

In this population of patients, 75%of whom were len refractory. The overall response rate was 78%. Median PFS was not reached with a nine-month PFS of 86%. Again, I think this is not surprising, but validates what a lot of us are doing, is using DPD as a second-line or third-line treatment.

I think these data compare fairly or similarly at least to the dara-bortezomib-dex data in the CASTOR trial. I think either of these are options for len refractory patients progressing after 1 or 2 prior lines of treatment.