|The following article features coverage from the American Society of Hematology 2020 meeting. Click here to read more of Cancer Therapy Advisor‘s conference coverage.|
An assessment of eligibility criteria in landmark clinical trials in multiple myeloma revealed that ineligibility rates were quite different among the trials, suggesting significant limitations of cross trial comparisons.
Augusta Eduafo, DO, of St. John Medical Center, Cleveland, Ohio, presented this trial analysis at the virtual 62nd American Society of Hematology (ASH) Annual Meeting and Exposition.
“The trial population is different from the real world mostly due to inclusion and exclusion criteria,” Dr Eduafo said. “Excessive or overly restrictive eligibility criteria can potentially lead to slowing of trial recruitment, can jeopardize the generalizability of results, and limit understanding of the intervention benefit-risk profile.”
This can lead to a gap between enrolled patients and real-world populations. For example, in myeloma, a large portion of patients suffer from different degrees of renal failure, but these patients may be excluded from clinical trials.
Dr Eduafo and colleagues assessed the eligibility criteria of 6 landmark myeloma studies. Four trials used lenalidomide-dexamethasone in the second line or later: ASPIRE, ELOQUENT-2, POLLUX, TOURMALINE-MM1. Two trials used bortezomib-dexamethasone: ENDEAVOR and CASTOR.
The researchers then identified 516 patients with relapsed disease at university hospitals receiving second- or later-line therapy and classified them as being “trial-eligible” or “trial-ineligible”. They excluded 153 patients due to missing values.
Trial-ineligible patients had significantly worse overall survival compared with eligible patients (hazard ratio [HR], 1.43; 95% CI, 1.08-2.02; P <.001). The 2-year survival rate was 69% vs 82%.
The patients eligible for the trials were more likely to have better renal function, autologous stem cell transplant, lower percentage of refractory disease to proteasome inhibitor (PI) or lenalidomide, and had longer treatment-free period before index treatment date, the researchers reported.
The most common things that excluded a patient from a trial were being refractory to PI, renal dysfunction, or the presence of other malignancies.
The ASPIRE trial had the highest threshold for renal function among the lenalidomide trials, with a creatinine clearance of greater than 50 mL/min. This caused a high rate of exclusion compared with the other trials (29% vs 8%, respectively). More than one-third of patients were excluded for being bortezomib-refractory in the TOURMALINE-MM1 and ASPIRE trials.
Disclosures: Some of the presenters disclosed financial relationships with the pharmaceutical industry and/or the medical device industry. For a full list of disclosures, please refer to the presentation abstract.
Read more of Cancer Therapy Advisor‘s coverage of the ASH 2020 meeting by visiting the conference page.
Eduafo A, Metheny L, Driscoll J, et al. Patient selection bias limits the real world efficacy of randomized clinical trials in multiple myeloma. Presented at 62nd American Society of Hematology (ASH) Annual Meeting and Exposition. December 5-8, 2020. Abstract 207.