Quality of Life during Survivorship Following Autologous Stem Cell Transplant for Mantle Cell Lymphoma

Introduction:

Consolidative autologous stem cell transplant (ASCT) in 1^st line treatment of MCL has become controversial. Despite durable disease control after intensive induction, ASCT entails short- and long-term risks, logistical challenges, and no clear overall survival benefit in the modern era. Recently, an early analysis of the TRIANGLE trial demonstrated no improvement in failure-free survival in patients with ASCT compared to ibrutinib-containing 1^st line therapy without ASCT. As consolidative ASCT is an individualized decision, it is crucial to understand patients' experiences including quality of life (QoL) and functional /work status during survivorship after ASCT for MCL. However, such data is very sparse in the literature. We examined QoL and employment after ASCT in patients with MCL from the long-term follow-up (LTFU) cohort at Fred Hutchinson Cancer Center.

Methods:

We reviewed annual survey data from adult patients who received ASCT for MCL. Survey items included patient-rated health/QoL in general, Patient-Reported Outcomes Measurement Information System-29 v2.0 (PROMIS-29), and cognitive function- short form 4a v2.0 (PROMIS-CF). PROMIS-29 measures physical and mental health, and symptoms. The domain raw score is rescaled to a T score, which has a mean of 50 and standard deviation of 10 in the US general population. A score difference of 10 is generally considered as the minimal important difference (MID), the smallest difference meaningful to patients. We performed descriptive analyses of the baseline characteristics, employment, and QoL. We explored the association between impairment of the measured domains and employment by univariable Chi-square test.

Results:

Among the 168 MCL patients receiving ASCT identified in the LTFU cohort, 106 completed ≥1 survey, and were the subjects of primary analysis. Baseline characteristics were similar between respondents and non-respondents. Among respondents, the median age at ASCT and at response to the survey was 59 and 68 years, and 79% were men. Transplants were performed between 2000 and 2023, 66% received ASCT after 2010, all had only one transplant, and 75% reported being in remission (9.4% with relapse, 16% unknown) at the time of the survey. Median follow-up from ASCT was 9.3 years. Median overall survival was not reached.

Among the respondents, 76%-87% rated their overall health, QoL, physical health, mental health/ability to think, social activities/roles, and satisfaction with social activities/roles to be “good”, “very good”, or “excellent”. The average PROMIS T scores were similar to the general population in all domains (mean: 46-50). However, compared to the general population, 18% and 16% patients reported poorer physical and cognitive function (T score<40), and 5%-12% had more symptoms of anxiety, depression, fatigue, sleep disturbance, and pain (T score>60); 40% had impairment in ≥1 domain, which was similar based on interval from ASCT (≤5 vs. 5-10 vs. >10 years). Patients remaining in remission had numerically better QoL, compared with those not in remission or with unknown status. Approximately 34% of patients worked full or part time, and this rate was numerically higher in patients ≤65 years (23/33, 70% vs. 13/73, 18%) and in those in remission (37% vs. 26%). Considering patients in remission, those with decreased physical function (odds ratio [OR]: 0.12, 95% confidence interval [CI]: 0.05, 0.69) and with impairment in any domain (OR: 0.28, 95% CI: 0.07, 0.89) were significantly less likely to work. Findings were similar when a MID of 5 was applied.

Conclusions:

In this largest study with the longest follow-up of QoL after ASCT for MCL, we showed that close to one fifth of patients experienced decreased physical function and two fifths had impairment in ≥1 aspect of QoL even among long-term survivors. Our data suggest a link between physical function and overall impairment with employment. These findings suggest consolidative ASCT may impact physical and cognitive function in a significant subgroup of MCL patients, and highlights the need for larger studies incorporating patient experience alongside traditional outcomes measures, to inform shared medical decision making.

Di:BeiGene: Consultancy, Research Funding; Schrodinger, Inc.: Research Funding. Smith:Merck Sharp and Dohme Corp: Research Funding; BMS (spouse): Research Funding; Millenium/Takeda: Consultancy; Coherus Biosciences (spouse): Consultancy; Bayer: Research Funding; Beigene: Consultancy, Research Funding; ADC therapeutics: Consultancy, Research Funding; Incyte: Consultancy, Research Funding; Karyopharm: Consultancy; AstraZeneca: Consultancy, Research Funding; Lumanity: Consultancy; De Novo Biopharma: Research Funding; Kymera Therapeutics: Research Funding; Enterome: Research Funding; Ignyta (spouse): Research Funding; Epizyme: Consultancy; Genentech: Consultancy, Research Funding; KITE pharma: Consultancy; abbvie: Consultancy. Shadman:Kite Pharma: Consultancy; Merck: Consultancy; Fate therapeutics: Consultancy; Nurix: Consultancy; Eli Lilly: Consultancy; Bristol Myers Squibb: Consultancy; AbbVie: Consultancy, Research Funding; Mustang Bio: Research Funding; Vincerx: Research Funding; Koi Biotherapeutics: Current holder of stock options in a privately-held company; BeiGene: Consultancy, Research Funding; Janssen: Consultancy; Morphosys/Incyte: Consultancy, Research Funding; Genmab: Consultancy, Research Funding; Bristol Myers Squibb (spouse): Current Employment; AstraZeneca: Consultancy, Research Funding; Genentech: Consultancy, Research Funding. Ujjani:Abbvie, Astrazeneca, Beigene, Genentech, Jansen, Lilly, Pharmacyclics: Honoraria; AbbVie, Astrazeneca, Lilly, PCYC: Research Funding. Lynch:Merck: Honoraria; SeaGen, Foresight Diagnostics, Abbvie, Janssen: Consultancy; TG Therapeutics, Incyte, Bayer, Cyteir, Genentech, SeaGen, Rapt, Merck, Janssen: Research Funding. Poh:Ipsen: Consultancy, Membership on an entity's Board of Directors or advisory committees; Incyte: Research Funding; Seagen: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Dren Bio: Research Funding; Astex: Research Funding; Acrotech: Consultancy, Membership on an entity's Board of Directors or advisory committees. Till:Bristol Myers Squibb: Research Funding; Mustang Bio: Consultancy, Patents & Royalties, Research Funding. Warren:Roche Diagnostics: Other: Travel Support. Gopal:Merck: Consultancy, Honoraria, Research Funding; I-Mab bio: Research Funding; IgM Bio: Research Funding; Takeda: Research Funding; Gilead: Consultancy, Honoraria, Research Funding; Astra Zeneca: Research Funding; Agios: Membership on an entity's Board of Directors or advisory committees; Janssen: Consultancy, Honoraria, Research Funding; BMS: Research Funding; SeaGen: Research Funding; Teva: Research Funding; Genmab: Honoraria, Research Funding; Beigene: Consultancy, Honoraria, Research Funding; Incyte: Consultancy, Honoraria; Kite: Consultancy, Honoraria; Morphosys/Incyte: Consultancy, Honoraria; ADCT: Consultancy, Honoraria; Acrotech: Consultancy, Honoraria; Merck: Consultancy, Honoraria; Karyopharm: Consultancy, Honoraria; Servier: Consultancy, Honoraria; Cellectar: Consultancy, Honoraria; Compliment: Consultancy, Current holder of stock options in a privately-held company, Honoraria; Epizyme: Consultancy, Honoraria; Lilly: Consultancy, Honoraria; Caribou: Consultancy, Honoraria; Fresenius-Kabi: Consultancy, Honoraria; Scitek: Consultancy, Honoraria; Sana: Consultancy, Honoraria. Lee:nmdp: Membership on an entity's Board of Directors or advisory committees; Janssen: Research Funding; Novartis: Honoraria; Pfizer: Research Funding; Sanofi: Honoraria, Research Funding; Incyte: Honoraria, Research Funding; AstraZeneca: Research Funding.