Safety
Seven patients experienced disease progression and five died during induction, with one dying from disease progression, two deaths related to cardiac adverse events (AEs), and two related to other AEs.
In terms of safety, the most common grade 3-4 AEs were neutropenia (25%), thrombocytopenia (5%), and infections (7%).
Peripheral neuropathy was reported among 13% of patients at any grade, and less than 1% grade 3-4.
“Our findings confirm that six cycles of Isa-KRd induce exceptionally high response and MRD negativity rates, not only at a sensitivity of 10−5 but also at 10−6,” Perrot said.
She noted that, in comparison, the MRD negativity rate at 10−5 in the related CASSIOPEIA, GRIFFIN, and IsKia trials were 35%, 22%, and 45%, respectively.
“A longer follow-up is needed to better interpret the significance of achieving MRD negativity in patients with different cytogenetic abnormalities,” Perrot added.
“Importantly, the Isa-KRd induction ensures successful stem cell collection, with no new safety signals,” she said.
The Isa-KRd regimen is not yet approved, hence only used in clinical trials, but Perrot told this publication the current evidence should help change that.
“The IsKia trial is comparing KRd and Isa-KRd, and Sanofi should try to approve the combo,” she said. “We hope the Midas data will support this approval.”
Questions Aplenty Moving Ahead
While the results are just the first from the ongoing trial, interest in the study and its design is high, Joseph Mikhael, MD, chief medical officer of the International Myeloma Foundation, told this publication.
“To have a large trial algorithm that is based on response and in particular MRD is novel and reflects the power of MRD in myeloma,” said Mikhael, a professor of applied cancer research and drug discovery at the Translational Genomics Research Institute, City of Hope Cancer Center, Phoenix, Arizona.
“Although the results are preliminary, these kinds of trials can inform our approach to MRD testing and may result in more personalized and effective treatments for patients,” he said. “This may include the potential to de-escalate or even stop therapies that have historically been given for longer or provide more intense therapies for patients with inadequate response.”
“We know the biology of myeloma is ‘one size fits all’, so the design of our trials should reflect that heterogeneity.”
Further commenting on the research, the meeting discussant Sagar Lonial, MD, professor and chair of the Department of Hematology and Medical Oncology and the Anne and Bernard Gray Professor in Cancer at the Winship Cancer Institute of Emory University, Atlanta, Georgia, offered cautious optimism.
Referencing the tale of Midas in Greek mythology as having a “be careful what you wish for” lesson, Lonial pondered that, likewise, a question that may be considered regarding MRD is “whether this is in fact a gift — or could this be a curse that’s going to get us into trouble at some point down the road. I don’t know the answer.”
Some cautionary lessons include prior research indicating that patients with high-risk disease may achieve a complete remission early — but they lose remission earlier down the road, he noted.
Other considerations as the research moves forward: “Recognizing that MRD may in fact be more important than genetics — which is a premise of the current trial,” Lonial pondered. “Does MRD override genetics, or do they travel together?”
The study is ongoing, with future results expected in terms of ASCT vs no ASCT for patients with high and low risk, as well as single vs tandem ASCT.
The trial received financial support from Amgen, Bristol-Myers Squibb, and Sanofi. Perrot reported ties with Amgen, Bristol Myers Squibb, and Sanofi. Mikhael disclosed ties with Amgen, Bristol Myers Squibb, and Sanofi. Lonial reported relationships with Celgene, Bristol-Myers Squibb, Amgen, and Sanofi.
A version of this article first appeared on Medscape.com.