By Megan Brooks
NEW YORK (Reuters Health) - 23/5/2019
"We typically see two types of patients - those who are anxious and want to do something to prevent cancer from developing, and those who are more cautious and are willing to watch and wait. It's gratifying to know that especially for the first group of patients there may now be a viable treatment option," lead investigator Dr. Sagar Lonial of Winship Cancer Institute at Emory University, in Atlanta, said in a statement.
He discussed the findings during a press briefing May 15 ahead of presentation June 2 at the American Society of Clinical Oncology (ASCO) annual meeting in Chicago.
"This is the idea of trying to identify a precursor condition and potentially prevent the development of symptomatic cancer through early intervention, which I think was really a major goal we have had in this field for a long time," Dr. Lonial told the briefing. The phase 2/3 trial enrolled patients with intermediate or high-risk smoldering multiple myeloma. In phase 2 (testing potential efficacy), 44 patients received 25 mg of oral lenalidomide once daily on days 1 through 21 for every 28-day cycle, as well as 325 mg of aspirin on days 1 through 28, until disease progression or unacceptable toxicity. In phase 3, 90 patients received the same treatment regimen and 92 were observed (control arm). The median follow-up was 71 months in phase 2 and 28 months in phase 3.
The time to develop multiple myeloma was significantly delayed with lenalidomide. Three-year progression-free survival was 87% in phase 2 and 91% in phase 3 among patients receiving lenalidomide, versus 66% among people who did not receive the therapy and were just observed for potential progression in phase 3 (hazard ratio, 0.28; P=0.0005). However, a high proportion of patients could not tolerate lenalidomide, with 80% of patients in phase 2 and 51% of people in phase 3 discontinuing the medicine due to toxicity, the investigators report in their abstract.
Non-hematologic adverse events of grade 3 or 4 occurred in 28% of phase-3 patients on lenalidomide, with fatigue being the most common. High-grade neutropenia was seen in about 5% of people. There was no patient-reported difference in quality of life between those who took lenalidomide and those who did not.
The investigators are now doing an analysis of patients who stopped taking lenalidomide due to toxicity to see if even limited doses of the drug may have delayed progression to multiple myeloma.
Dr. Joshua Richter, a multiple myeloma expert at The Tisch Cancer Institute at Mount Sinai in New York City who was not involved in the study, told Reuters Health by email that "the majority of patients with smoldering disease in this country are followed with observation alone with a small percentage enrolling into interventional clinical trials. The findings of this study support an improvement in progression-free survival with an acceptable toxicity profile."
ASCO president and briefing moderator Dr. Monica M. Bertagnolli said this is a "very important study that covers an area that is a very important ASCO research priority which is identifying strategies to actually detect and treat premalignant lesions; this area of prevention rather than treatment is one where we have far too few successes and certainly need to see more, so congratulations" to the investigators, she told the briefing.