Tolerability and Efficacy of Post Transplant Lenalidomide Maintenance Therapy in Multiple Myeloma: A Real World Single Centre Experience

Introduction:

Lenalidomide maintenance therapy (LMT) post autologous stem cell transplant (ASCT) in multiple myeloma (MM) has been shown to improve PFS and has become a mainstay therapy. This study examines the tolerability and efficacy of LMT in a real world setting at Princess Margaret Cancer Centre (PMH).

Methods:

Retrospective review was done for consecutive patients (pts) who underwent ASCT at PMH from Jan 2012 to Jan 2015. Pts who started LMT and followed at PMH were included. Pts were excluded if: 1) diagnosis was not solely MM, 2) tandem or salvage ASCT, 3) on no or a different maintenance regimen, 4) on clinical trial, and 5) exclusively followed in the community. The following were collected for up to 36 months (mo): 1) duration of LMT, 2) dose delivered (calculated as % of standard dosing of 10 mg daily i.e. 280mg per 28 day cycle), 3) reasons for reduction or discontinuation, 4) toxicities (graded per CTCAE v4. Where clinical documentation not sufficient for grading, marked as grade 3/4 if dose reduction/discontinuation occurred), 5) secondary primary malignancies (SPM), and 6) patient reported outcomes (PRO) through the validated Edmonton Symptom Assessment Score (ESAS). PFS (calculated from start of LMT) and OS were collected until date of last follow up. Univariate analysis was done for subgroup analysis. Patient compliance on therapy was not able to be captured.

Results:

575 consecutive pts were screened. 119 pts were included with their characteristics in Table 1. Common reasons for exclusion include: followed exclusively in the community (200), no maintenance (92), different maintenance (58), tandem/salvage transplant (61).

The average duration on LMT was 33.2 mo (95%CI: 26.1-Not reached). The average starting dose was 80% of standard dosing with 48 pts (41%) starting below, 63 pts (54%) starting at the standard dosing, and 5 pts (4%) starting above. Average % dose delivered was as low as 53% by 30 mo follow up (Figure 1). The median time to first dose reduction (DR) was 6 mo (0.7-27mo). 59 pts (50%) required DR after starting LMT and common reasons were neutropenia (41%), other cytopenias (17%), fatigue (15%), rash (12%), diarrhea (5%), infection (3%), renal impairment (3%). No pts were dose escalated beyond 10 mg daily. For the 5 pts started at dose of 15mg daily, all eventually required DR to ≤ 10mg daily.

The most common clinical toxicity (any grade occurring at least once in each patient) include infection (66%), fatigue (58%), diarrhea (29%), rash (23%), muscle cramps (18%), peripheral neuropathy (15%), bleeding (12%), VTE (6%). The most common grade 3 and 4 hematologic toxicity include neutropenia (31%), thrombocytopenia (6%), anemia (1%).

There were 4 cases of SPM during LMT (SCC of skin at 6 mo, breast at 12 mo, colon at 18mo, MDS at 36 mo) and 1 case of cancer recurrence (bladder at 6 mo).

Over the study period, 53 (45%) pts discontinued LMT. Reasons included: 34 (64%) disease progression, 16 (30%) toxicity, 3 (6%) patient or clinician choice. Of the 16 pts discontinued due to toxicity, the reasons include cytopenia (5), fatigue (5), cancer (1), peripheral neuropathy (1), GI intolerance (1), MDS (1), pneumonitis (1), and infection (1).

PRO was collected in the domains of "tiredness", "drowsiness", "nausea", "appetite", "shortness of breath", "depression", "anxiety", and "wellbeing" (Figure 2) on a scale of 0 to 10. Highest (worst) scores were reported in the categories of "tiredness" and "wellbeing". The scores in each domain remained stable during the follow up period, with "appetite" statistically significantly improved (p=0.025).

The median PFS was 41.7 mo (95% CI: 30.1- Not reached). There were 2 reported deaths. There were no difference in PFS between those who did and did not require dose reduction (p=0.235). Difference in PFS was statistically significant based on ISS stage (p=0.008). There were no subgroup differences based on gender, type of MM, or response to ASCT. OS was not reached.

Conclusion:

In this real world experience of LMT in MM, few pts were able to achieve a dose of 10mg daily with 70% of pts requiring dose reduction by 36 mo and 13% discontinuation of therapy due to side effects. Nonetheless, this did not have significant impact on PRO and a PFS was achieved of 41.7 mo which is comparable to clinical trials. This study confirms efficacy and tolerability of LMT in a real practice setting. Maintenance lenalidomide should be encouraged for all post-ASCT pts even if at reduced doses.

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