Effect of Thalidomide with Melphalan and Prednisone on Health-Related Quality of Life (HRQoL) in Elderly Patients with Newly Diagnosed Multiple Myeloma: A Prospective Analysis In a Randomized Trial

Abstract

2972 Thalidomide (T) with melphalan/prednisone (MPT) was defined as a standard treatment in elderly patients with multiple myeloma (MM) based on 5 randomized trials. Treatment with MPT not only showed improved response rate, significantly better time to response as well as quality of response but also a significant improvement of event free survival (EFS), progression free survival (PFS) and overall survival (OS). In one of these trials, HOVON 49, a prospective Health related – Quality of life (HRQoL) was initiated in order to asses the impact of T on QoL. (Wijermans et al, J Clin Oncol 28:3160-6). Patients aged >65 years with newly diagnosed symptomatic MM were randomized to receive 8 cycles of MP or MPT, followed by T maintenance in MPT arm. 284 patients were included in this HRQoL side study (MP: n=149, MPT: n=135). HRQoL was assessed with the EORTC core QoL Questionnaire (QLQ-C30) and the myeloma-specific module (QLQ-MY24) at baseline and at pre-determined intervals during treatment. Treatment-related toxicity WHO grade 2–4 occurred in 60% of MP and 87% of MP-T treated patients. Most frequently found were neutropenia-related infections, neurotoxicity (mostly T induced peripheral neuropathy) and myelotoxicity. The QLQ-C30 subscales Physical Function (p=0.044) and Constipation (p<.001) showed a treatment related improvement during induction in favour of the MP arm. During T maintenance, the scores for the QLQ-MY24- Paraesthesia became significantly higher in the MPT arm (p<.001). The QLQ-C30 subscales Pain (p=0.12), Insomnia (p=0.068), Appetite loss (p=0.074) and the QLQ-MY24- item Sick (p=0.086) scored marginally better during T maintenance. The overall QoL scale QLQ-C30-HR-QOL showed a significant time trend towards more favourable mean values during protocol treatment but did not reveal differences between MP and MPT. For the QLQ-C30 subscales Emotional function and Future perspectives, difference in favour of the MPT arm from the start of treatment was observed (p=0.018and p=0.045 respectively) with no significant ‘time × arm' interaction, indicating a persistent better patient perspective with MPT treatment. Since the first questionnaire was filled out prior to treatment but after randomization we hypothesise that the awareness of being treated with a medication that holds out a prospect of better treatment outcome may in itself be associated with improved feeling of well-being and hope for the future. This prospective study shows that the higher frequency of adverse effects associated with MPT does not translate into a negative effect on HRQoL and that MPT holds a better patient perspective. Disclosures: No relevant conflicts of interest to declare.

Quality of life during and following sequential treatment of previously untreated patients with multiple myeloma: findings of the Medical Research Council Myeloma IX randomised study

“…The VISTA trial (Delforge et al , ) reported that QoL was comparable between the two arms (bortezomib and MP (VMP) versus MP) after approximately 1 year in a population similar to the non‐intensive pathway. The finding that thalidomide maintenance therapy has little impact on QoL is consistent with an earlier study (Verelst et al , ) and the combination of lenalidomide and low‐dose dexamethasone (RD) versus MPT has been reported to improve OS without having a negative effect to QoL (Delforge et al , ).…”

“…This raises the question, what is more important: a large change in an individual scale, or multiple small changes across key subscales that are maintained over time? Alternative definitions of a MID, whether it be ≥5 points (Kvam et al , ; Verelst et al , ; Delforge et al , ), subscale specific (Cocks et al , ; Dimopoulos et al , ; Delforge et al , ), or ≥10 points, as used in this work, makes comparison between studies very difficult and research less meaningful. A consensus on such measurements is clearly required.…”

Health‐related quality of life and disease‐specific complaints among multiple myeloma patients up to 10 yr after diagnosis: results from a population‐based study using the PROFILES registry

“…While some studies report on the influence of a particular MM treatment on HRQOL, which helps patients and doctors making an informed treatment decision , others compared HRQOL across different treatments modalities, usually resulting in one favorable treatment option . Furthermore, some studies compared patients with MM with the general population and concluded that patients with MM had a significantly impaired QOL .…”

Diffuse large B-cell lymphoma and multiple myeloma in elderly patients

“…48,49 Several studies investigating the effect of treatment with melphalan and prednisone in combination with bortezomib, lenalidomide or thalidomide in elderly patients found improvement of HRQOL during treatment. [50][51][52][53][54][55] Nevertheless, although HRQOL improved during treatment, it was still markedly reduced in comparison to the normative population. 49 Also in this thesis we observed that MM patients of both age categories experienced a high symptom burden.…”

“…At last, multiple studies observed an association between varying domains of CGA and treatment toxicity and survival. [53][54][55][56][57][58][59] However, also these trials oftentimes included small numbers of patients and the exact method of CGA differed between the several trials. Several trials focused specifically on the role of CGA in patients with aggressive B-cell lymphoma.…”