Oncology Experts Highlight Practice-Changing Abstracts at ASH 2017

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

Using 2 agents approved in the Hodgkin lymphoma landscape, a phase I/II trial is investigating the combination of brentuximab vedotin (Adcetris) and the PD-1 inhibitor nivolumab in patients with relapsed/refractory classical disease, an area said to be one of unmet medical need (NCT02572167). Adult patients enrolled progressed on frontline chemotherapy regimens.

“This abstract has been presented multiple times in the past,” Younes recalled. “These are merely updates with more patients and more follow-ups. It is very interesting because this is a chemotherapy-free regimen and just 2 drugs, so when you get to transplant, you’re probably in better shape [because you’re] not beaten up by chemotherapy. It’s very impressive. As you know, this doublet has been moved to a randomized trial in the posttransplant setting, which is seeking approval, so now the randomized trial is this doublet, compared to the standard brentuximab alone.” Younes

Safety and efficacy of atezolizumab (Tecentriq) in combination with obinutuzumab (Gazyva) and bendamustine in patients with previously untreated follicular lymphoma: an interim analysis (Abstract 481)

Interim findings of a cohort from a phase I/II study will be presented looking at the safety and efficacy of induction therapy with obinutuzumab and bendamustine plus the PD-L1 inhibitor atezolizumab, followed by maintenance treatment with obinutuzumab and atezolizumab in patients with treatment-naïve follicular lymphoma (NCT02596971). Previously, findings from the phase III GALLIUM trial demonstrated significant improvement with obinutuzumab in combination with bendamustine, thus the mechanistic effect of PD-L1 to the immune system could further improve responses.

“That’s where the field is heading right now, to incorporate these new agents that may not have overlapping toxicities with frontline regimens,” said Younes. “Atezolizumab is a PD-L1 antibody. I’m not interested in the concurrent administration, I’m interested in the adjuvant or maintenance setting because these agents may have a better chance of eradicating minimal residual disease (MRD) compared with a passive immune therapy like a CD23[-antibody].”

Initial treatment with lenalidomide (Revlimid) plus rituximab for mantle cell lymphoma: 5-year follow-up and correlative analysis from a multi-center phase II study (Abstract 154)

Previously, results of this phase II study had shown an overall response rate (ORR) of 92% and a CR rate of 64% in patients with MCL; the regimen was also found to be well tolerated (NCT01472562). The long-term findings will include 5 years of follow-up and an exploratory analysis of immunologic biomarkers and measurement of MRD.

“We are going to move away from chemotherapy gradually, and we’ll use less and less stem cell transplant upfront,” Younes explained. “That’s my prediction. It is very intriguing that you can achieve a 4-year PFS of 70%, and OS at 5 [years] is more than 80%. We used to think the median survival of patients was 7 years, so this is clearly a great option for patients.”

LEUKEMIA

Ivosidenib (AG-120) in mutant IDH1 AML and advanced hematologic malignancies: results of a phase I dose escalation and expansion study (Abstract 725)

This is the first-in-human, phase I study of ivosidenib, a potent, selective, oral, small-molecule inhibitor of the mutant IDH1 protein in patients with IDH1-mutant advanced hematologic malignancies, including relapsed/refractory acute myeloma leukemia (AML; NCT02074839). Data will include results from 4 expansion cohorts, which comprise a total of 258 patients. Researchers investigated safety, MTD, pharmacokinetics, and pharmacodynamics.

 
Alexander Perl, MD
Alexander Perl, MD
“This, like enasidenib (Idhifa), is a drug that [researchers] were able to dose escalate from very low doses to very high doses,” explained Alexander Perl, MD, member of the Leukemia Program in the Abramson Cancer Center and an associate professor in the Division of Hematology/Oncology at the Perelman School of Medicine at the University of Pennsylvania.

“From 100 mg all the way up to 1200 mg, they found no obvious dose-limiting toxicity along the way and picked a median dose to move forward because they had a biomarker to say they were inhibiting the target of the drug and reducing this byproduct of the IDH2 mutation called 2HG. They do not see an obvious drug-associated toxicity profile at this dose, but they do see differentiation syndrome with this drug as they did with enasidenib. It looks very promising, and I know that this drug is poised to be submitted very soon to the FDA for review based on these data.


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