Oncology Experts Highlight Practice-Changing Abstracts at ASH 2017

Gina Columbus @ginacolumbusonc
Published: Thursday, Dec 07, 2017

“What they had done was they stratified the data by response in the 2 arms, and they had preliminary data at that time showing that MRD negativity was achieved in both arms,” explained Landgren. “There were more people in the transplant arm than in the other arm, but if you were MRD negative, there was very similar PFS. That’s exactly what this new abstract is looking at. Now that we are taking it to the new level, they have new sequencing data. This is important; it really pushes the field [forward] even more.”

Effect of autologous hematopoietic stem cell transplant (aHSCT) on the development of second primary malignancies (SPM) in multiple myeloma patients (Abstract 332)

SPMs are a common development for patients with multiple myeloma; moreover, prior studies of patients who underwent aHSCT have calculated standardized incidence ratios versus the general population, but have not compared the cumulative incidence of SPMs among patients with myeloma undergoing aHSCT to those who do not. This is a direct comparison of the effect of aHSCT on the incidence of SPMs in patients with multiple myeloma.

“This looks into patients treated with and without transplant upfront and they look at 5 and 10 years of cumulative incidence,” Landgren said. “They show that at 5 and 10 years of follow-up, the cumulative incidence of secondary malignancies are 4% versus 7% in the nontransplant versus transplant patients. You double the rate of secondary malignancies in these patients. The particular increase is in the patients transplanted with regard to hematologic malignancies. That might be a reason for thinking about other therapies.”

Overall survival (OS) of patients with relapsed/refractory multiple myeloma (RRMM) treated with carfilzomib, lenalidomide, and dexamethasone (KRd) versus lenalidomide and dexamethasone (Rd): final analysis from the randomized phase III ASPIRE trial (Abstract 743)

Previously, ASPIRE demonstrated that the addition of carfilzomib to Rd is associated with a significant improvement in PFS compared with Rd alone in patients with RRMM, with a median PFS of 26.3 and 17.6 months, respectively. At the time of the PFS analysis, OS data were immature, but this planned final analysis of ASPIRE will include OS results.

“This is showing that the OS is significantly better with the 3-drug combination,” Landgren explained. “Previously, it was only for PFS; now, they show that the hazard ratio is 0.79. There is a 21% reduction in the risk of death, and the median OS is 48 versus 40.4 months.”

Daratumumab, lenalidomide, and dexamethasone (DRd) versus lenalidomide and dexamethasone (Rd) in relapsed or refractory multiple myeloma (RRMM): Updated efficacy and safety analysis of POLLUX (Abstract 739)

The pivotal phase III POLLUX trial was one of 2 studies that were the basis for the FDA approval of daratumumab in combination with lenalidomide and dexamethasone or bortezomib (Velcade) and dexamethasone for patients with relapsed multiple myeloma following at least 1 prior therapy in November 2016. When the prespecified interim analysis of POLLUX was presented at a median follow-up of 13.5 months, the triplet of daratumumab, lenalidomide, and dexamethasone was found to reduce the risk of disease progression or death by 63% and significantly improved the ORR versus Rd alone. This analysis will include updated efficacy and safety data in POLLUX based on longer follow-up.

“They do not have OS data, but they have extended follow-up and the follow-up goes, this time, up to 33 months,” Landgren said. “That previously was 18 months. It holds up, and none of the 2 arms have yet met the median for PFS. That is also a very interesting combination for sure.”

Durable clinical responses in heavily pretreated patients with relapsed/refractory multiple myeloma: updated results from a multicenter study of bb2121 anti-BCMA CAR T cell therapy (Abstract 740)

The CRB-401 study (NCT02658929) is a multicenter phase I dose escalation trial of bb2121 in patients with relapsed/refractory myeloma who have received more than 3 prior regimens, including a proteasome inhibitor and an immunomodulatory agent, or are double-refractory, and have more than 50% BCMA expression on malignant cells. This study’s initial findings were the basis for the FDA granting a breakthrough therapy designation for this patient population in November 2017.

“Similar to what we heard from in the other disease areas, the numbers are relatively small and the follow-up time is restricted,” Landgren said. “There are ongoing clinical trials using different CAR T cells targeting BCMA in myeloma. They all showed very similar findings that the therapy seems to work if you go into higher doses; bb2121 has less of [CRS] and, reportedly—numbers were so small—but there were some patients who were followed for up to 1 year that persisted in CR. It is exciting, but we need to see more data.”

To view the full "Pre-Conference Perspectices on Hematologic Malignancies" series, visit https://www.onclive.com/inside-oncology/pre-conference-heme2017.

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