The largest real world study of ASCT outcomes in elderly patients shows the therapy is safe and results in similar long-term outcomes as those experienced by younger patients undergoing the treatment.
Investigators say ASCT eligibility for patients aged 70 years and over should be based on biological age, performance status and comorbidities, and not on chronological age alone.
The study, published in Internal Medicine Journal, reports on outcomes from 421 MM patients who underwent ASCT at Peter MacCallum Cancer Centre and University Hospital Geelong, Victoria, between 2008 and 2016.
Some 300 patients were in the younger group (<65 years) and 121 in the elderly group (≥65 years) with no significant difference between the two groups in terms of sex, myeloma subtype, ISS stage or cytogenetics/FISH results.
Speaking to the limbic oncologist at Peter Mac and lead author Dr Jeremy Er said ASCT uptake had traditionally been low among patients in the elderly age group because of concerns about the toxicities of transplant and doubts that patients older than 70 may not benefit from or tolerate transplant.
“The early trials were done in patients below age 65 and that’s why there may be some hesitancy offering ASCT to elderly patients. We suggest it’s viable up to age 75 based on our findings – obviously that comes with being biologically fit. Most centres wouldn’t transplant someone above age 75 but the data out there is showing, more and more, that it is feasible in at least above age 70 and rates of transplantation in the group are increasing.”
Dr Er said response rates post-ASCT did not differ significantly between elderly and younger patients with approximately a third of patients in both groups achieving a complete response.
Meanwhile, the median time to neutrophil engraftment was similar in both groups – 11 days in the younger group compared to 12 in the elderly (P = 0.456), while platelet engraftment also did not differ (11 days in both groups, P = 0.447).
Transplant-related mortality (TRM) was low at 1.67% for the young and 2.48% for the elderly group over a median follow up of 68 months.
While there were no significant differences in response rates between the two groups post transplantation – younger patients had 57% three-year PFS survival compared to 45% in the elderly group – there was a statistically significant prolongation of median PFS in the younger group (40 months vs 31 months, P = 0.026).
OS was 82% for both groups, with a trend towards increased OS in the younger group that was not statistically significant. (116 months vs 74 months, P = 0.184).
Dr Er speculated that the observation likely reflected the use of reduced treatment intensity because of tolerability concerns, presence of comorbidities and lack of exposure to subsequent lines of salvage therapy at progression.
“While dose reduction of melphalan has been an approach to decrease TRM in the elderly, 70% of patients in the elderly group in our study received full dose (200 mg/m2) melphalan with 13 out of 25 patients aged ≥70 years receiving full-dose melphalan and no TRM,” he said.
Caution over selection
But he remained cautious about applying the finding more broadly to elderly patients undergoing ASCT.
“These findings should still be interpreted with caution as patients ≥70 years are likely to have more comorbidities and post-transplantation complications, so the patients on full dose melphalan in this study would have undergone careful selection prior to transplantation”.
Elderly patients receiving reduced dose melphalan (≤180 mg/m2 ) did not experience inferior PFS (33.5 months vs 31 months for patients receiving full-dose, P = 0.587), while the median OS was 61 months in those receiving reduced-dose melphalan and was not reached in the full-dose category (P = 0.102).
Dr Er said the finding showing PFS advantage in the elderly with ASCT should be reassuring, adding that ASCT eligibility in the elderly should be considered using biological age, along with performance status and organ function.
The use of objective risk-assessment scores such as the R-MCI or haemopoietic cell transplantation-specific comorbidity index (HCT-CI), easily accessible through a web calculator, could help to guide treatment decisions and risk–benefit ratios for each patient, he said. The European Myeloma Network recommended that patients with one or more risk factors present should have dose reduction of melphalan considered, he added.
Other factors to consider included prior tolerability of therapies and social issues relating to post transplant care.
Standard of care
As to whether ASCT will continue to be the standard of care in multiple myeloma in the era of highly active anti-MM therapies, Dr Er said clinical trials were needed to determine whether therapeutic combinations incorporating monoclonal antibodies would have comparable or superior efficacy over ASCT in the treatment of fit, elderly patients.
He also noted that while the chemotherapy-based MAIA trial recently showed that the addition of daratumumab to lenalidomide and dexamethasone had excellent early results, this drug combination was not currently reimbursed in all jurisdictions.
“Until then our observations support the use of ASCT as a standard of care for MM patients up to the age of 75 years who are considered fit enough for the procedure,” he concluded.