As a sub-analysis of HMR-MM-001 study, this study provides promising findings regarding the evolution of QoL and its association with cGVHD in patients with MM. More specifically, we report that allogenic HCT does not impact general QoL negatively, except for cognitive functioning QoL. However, QoL was associated to specific cGVHD symptoms, for which therapeutic actions can be implemented.
Overall, our observations highlight that nonmyeloablative allogenic HCT followed by bortezomib maintenance is associated with good levels of QoL. This is coherent with part of the literature showing that QoL scores are not significantly impaired by allogeneic HCT35. However, it should be noted that despite the absence of statistically significant differences, minimal differences in the evolution of QoL scores should be kept in mind 29. This particular point should be questioned during consultation given a gap between physicians’ and patients’ evaluations of symptoms16. The patients in this study declared few symptoms and presented with increasing emotional well-being after transplant. This improvement in emotional well-being can be linked with the fact that anxiety rate tends to be increased before allogeneic HCT and to decrease thereafter30. However, overall negative emotional symptoms are observed during the treatment course 31. In that sense, the absence of decline in QoL scores could be associated to the emotional specificity of the studied population. Indeed, it has been observed that declining QoL is associated with general symptom level and the presence of emotional distress as anxiety,, which are low in the case of nonmyeloablative, i.e. low-toxicity, HCT in highly selected and participants19.
Although global scores of QoL did not change significantly at different times points, they were nevertheless associated with GVHD symptoms. This observation is coherent with the literature showing that patients with higher GVHD symptoms report significantly lower QoL as measured with FACT-G and FACT-BMT than patients with lower or no GVHD16,17. Moreover, cognitive dysfunctions are reported by patients in this study. This seems to be a common symptom in patients with MM, notably following autologous32,33 and allogeneic34 HCT (see also35), and potentially exacerbated by GVHD and subsequent treatments36. The comparison of GVHD symptoms scores between patients formally diagnosed with cGVHD and those who were not showed only occasional differences. As observed in this study, GVHD symptoms seem to be overrepresented as they correspond to patients’ self-reported results rather than evaluation with NHS criteria. This observation points out the fact that a particular attention should be given to the patients’ evaluation of GVHD symptoms and their impact given the heterogeneity of experiences that can be retrieved in clinical care, suggesting that both subjective (i.e., patient-reported) and objective (i.e., clinical examination) should be implemented to tailor patient care37.
Given the potential influence of psychological variables on QoL and both autologous and allogeneic HCT outcomes (e.g., recovery, mortality)38, it appears crucial to develop interventions that target them. Among existing interventions, a palliative intervention based on physical and psychological symptoms management (i.e., addressing symptoms by pharmacological and behavioral means) showed positive results regarding the QoL along the disease, as well as the presence of anxio-depressive and symptoms burden after 2 weeks. After 3 months, QoL scores were higher and scores of depression lower in patients having benefited from the intervention compared to control group39. In a diversified population of hematological disease beneficiating from of either autologous or allogeneic HCT, a mindfulness intervention (i.e., aiming at being present to present experiences without being judgmental) showed positive results for QoL, depression, and anxiety immediately after the intervention and lessened after a 3 months follow-up40. Another intervention in patients with miscellaneous hematological malignancies, comprising three steps (i.e., watchful waiting, an internet-based self-help intervention, and individual face-to-face counseling or pharmacological treatment) showed no significant results and outcomes of interest (i.e., QoL, anxiety, and depression)41. The literature on interventions specifically targeted on patients with MM after stem cell transplant seems not consensual, remains scarce, and encompasses considerable limitations42. Thus, it appears crucial to mobilize a solid methodological framework to develop and evaluate tailored interventions aiming at increasing well-being and better QoL in patients with MM in a context of HCT. Given the findings of the present study, future interventions should take different variables into account, such as cognitive impairment or fatigue to deal with adverse effects induced by treatments.
To go further on potential psychosocial interventions, as the literature suggests, future studies should take subjective variables into account when considering the potential effects of treatments on QoL in patients with MM. Anchoring it more in theoretical models, it seems that information, symptoms perceptions, or appraisals of illness and treatments could be considered as potentially influencing variables. For instance, it has been shown that a substantial part of patients declare misconceptions about the prognosis of MM and its curability, resulting in considerable psychological distress and impacting QoL12. On a broader population, it has been observed that patients reported overoptimistic conception of the effect of autologous HCT43. In the same vein, a study showed that patients’ perception of autologous transplant was predictive of their coping strategies and emotional distress44. In that sense, mobilizing theoretical models that imply those variables (e.g., the common-sense model of illness representation45–48) could be a path to understanding the different processes conducting to the evolution of QoL, identify profiles of at-risk patients, and consider developing targeted interventions.
This study comprises some limitations that lead to interpret the results with caution. First, it should be considered that the repeated measures at several times imply missing items due to constraints of the patientcare. For this reason, some scores could be underestimated. To address this point, it is proposed that questionnaires could be administered electronically to bring more flexibility in their completion. Secondly, due to the highly specific population and study design (phase II clinical trial), the sample size in this study remains small, without a control sample, leading to keep from generalization of the findings. Relative to the sample, its constitution can be a limitation in that it is mostly composed of educated Caucasian patients whereas it has been observed that MM is more frequent in African-American patients49. Thus, a study with a more diversified and larger sample size is needed to confirm our results. Doing so, different statistical methods could be carried out to ensure a sufficient statistical power and allow for more in-depth analysis. Eventually, the respective impact of the different symptoms (e.g., pain, fatigue) and treatments (e.g., painkillers) should be considered as potential moderators of the links between MM treatments and QoL.
The findings of this study bring interesting elements to reassess the care of patients with MM following allogeneic stem cell transplant and bortezomib maintenance. It is observed that global QoL is not impacted by those treatment but that some subfactors are, notably in relation in GVHD symptoms. Despite the limited sample size and the relatively straightforward nature of the analyses conducted, this study yields valuable insights into the links between QoL and GVHD following allogenic stem cell transplant. In that sense, a particular attention should be paid to them in patientcare. Further studies should address recruit broader samples, lead comparative analysis across the clinical profiles that could be encountered in the field, and consider other psychosocial variables that could modulate the impact of treatments on QoL in patients with MM.