Study Examines Fixed-Duration Therapy in Patients With MM Ineligible for Transplants

Continuous therapy is likely the best choice for most patients with newly diagnosed transplant-ineligible multiple myeloma (MM), but a new study says treatment-free intervals might be a good option for some patients, provided the first-line therapy is effective.

MM tends to affect the elderly. As many as 45% of new cases diagnosed in the United Kingdom are cases in which the patient is at least 75 years old. Three in 10 patients with MM are considered frail, meaning their ability to withstand grueling treatment is limited.

At the same time, new advancements in the treatment of the incurable disease are making it possible for more people to live without the cancer progressing.

Continuous lenalidomide and dexamethasone has been shown to boost progression-free survival, as has continuous daratumumab with bortezomib, melphalan, and prednisolone (D-VMP). Newer research has suggested daratumumab with lenalidomide and dexamethasone is also an effective treatment.

The combination of an elderly population with new, effective treatment options presents a conundrum for some patients and their physicians: What is the best way to maintain or boost quality of life for these patients given the incurability of the disease? In some cases, physicians and patients opt for fixed-duration therapy, with treatment-free intervals (TFIs). In other cases, treatment interruptions prove necessary due to toxicities.

In a study published this month in PLoS One, a team of British researchers attempts to understand the results of using TFIs in MM therapy.

“In view of the recent shift towards continuous therapy, we looked to evaluate the TFI as an additional metric of efficacy in routine practice, after 1st and subsequent lines of therapy, in a large cohort of [treatment-ineligible, newly diagnosed MM] patients,” wrote corresponding author Faouzi Djebbari, MPharm, MSc, of Oxford University Hospitals, in the United Kingdom.

To better understand the impact of treatment intervals, Djebbari and colleagues looked at a data set from the UK Thames Valley Cancer Network, identifying patients with treatment-ineligible, newly diagnosed MM who underwent at least 1 cycle of systemic chemotherapy between the years 2009 and 2017. Patients who had been involved in clinical trials were excluded, leaving a total of 292 subjects. The investigators wanted to evaluate the length of treatment intervals, and also compare it with overall survival rates and progression-free survival rates.

Two-thirds of patients (67%) in the cohort responded to first-line therapy. After that round, the median TFI was 6.9 months. However, after the second round of therapy, the TFI dropped to just 1.8 months. After the third round, TFIs were just 0.6 months.

Overall survival (OS) in the cohort was 30.2 months, and progression-free survival (PFS) had a median length of 9 months, though that statistic varied based on the therapy chosen. The data showed that patients over 75 had inferior OS and PFS rates compared to patients aged 75 and younger.

Djebbari and colleagues conclude that continuous therapy is preferable to fixed-duration therapy for most patients, and thus providers ought to shift toward the former.

“However, when continuous therapy is not appropriate due to patient choice, or toxicities leading discontinuation, an efficacious (not limited to thalidomide or bortezomib) but tolerable FDT strategy remains a reasonable alternative approach, which can produce a meaningful TFI,” they write.

Reference

Djebbari F, Sharpley FA, McLain-Smith S, Vallance G, Eyre TA, Kothari J, et al. (2020) Treatment-free interval as an additional measure of efficacy in a large UK dataset of transplant ineligible myeloma patients. PLoS ONE 15(2): e0229469. https://doi.org/10.1371/journal.pone.0229469