Krishna V. Komanduri

Background/Objectives: Autologous stem cell transplantation (ASCT) remains a standard frontline treatment for eligible patients with multiple myeloma and is associated with improved progression-free survival and sustained treatment responses. In addition to medical eligibility factors, pre-treatment psychosocial variables such as depression and anxiety as well as cognitive functioning may influence short- and long-term transplant outcomes. This study examined the relationship between pre-transplant psychosocial and cognitive functioning and clinical outcomes in patients with multiple myeloma undergoing ASCT. Methods: Participants (n = 245) undergoing a standardized protocol for ASCT in Miami, Florida received pre-transplant psychosocial and neuropsychological assessments. Patient-reported clinical variables and cognitive performance were related to transplant success and transplant recovery outcomes, including time to engraftment, length of hospital stay post-engraftment, and survival across four timepoints. Results: While most patients achieved engraftment within a similar timeframe, the duration of hospitalization following engraftment varied considerably. Only higher baseline trait anxiety was associated with longer post-engraftment hospital stays. In multivariate Cox regression analyses, post-engraftment length of stay was independently associated with long-term mortality when modeled as a continuous variable. In a secondary analysis using an empirically derived cutoff corresponding to stays longer than the 80th percentile (≥7 days post-engraftment), both prolonged post-engraftment hospitalization and poorer baseline delayed memory was independently associated with mortality. Descriptive survival analyses further showed that patients with prolonged post-engraftment hospitalizations had higher overall mortality and shorter survival than those with shorter post-engraftment hospital stays. Conclusions: Patients who demonstrated poorer delayed memory performance pre-transplant and prolonged hospital admission post-transplant may be most vulnerable to dying when examined at long-term follow-up. Pre-transplant psychiatric assessments provide an opportunity to identify and potentially implement supportive care interventions for patients at increased risk for cognitive impairment.

Background/Objectives: Autologous stem cell transplantation (ASCT) remains a standard frontline treatment for eligible patients with multiple myeloma and is associated with im-proved progression-free survival and sustained treatment responses. In addition to medi-cal eligibility factors, pre-treatment psychosocial variables such as depression and anxiety as well as cognitive functioning may influence short and long-term transplant outcomes. This study examined the relationship between pre-transplant psychosocial and cognitive functioning and clinical outcomes in patients with multiple myeloma undergoing ASCT. Methods: Participants (N = 245) undergoing ASCT in Miami, Florida completed routine pre-transplant psychosocial and neuropsychological assessments. Patient-reported clini-cal variables and cognitive performance were examined in relation to transplant success and transplant recovery outcomes, including time to engraftment, length of hospital stay post-engraftment, and survival across four timepoints. Results: While most patients achieved engraftment within a similar timeframe, the duration of hospitalization follow-ing engraftment varied considerably. Higher baseline trait anxiety was associated with longer post-engraftment hospital stays. In multivariable Cox regression analyses, post-engraftment length of stay was independently associated with long-term mortality when modeled as a continuous variable. In a secondary analysis using an empirically de-rived cutoff corresponding to stays longer than the 80th percentile (≥7 days post-engraftment), both prolonged post-engraftment hospitalization and poorer baseline delayed memory were independently associated with mortality. Descriptive survival analyses further showed that patients with prolonged post-engraftment hospitalizations had higher overall mortality and shorter survival than those with shorter post-engraftment hospital stays. Conclusions: Patients who demonstrated delayed memory performance pre-transplant and prolonged hospital admission post-transplant may be most vulnerable to dying when examined at long-term follow-up. Pre-transplant psychiatric assessments provide an opportunity to identify potentially implement supportive care interventions for patients at increased vulnerability for cognitive impairment.

Supplementary Methods Supplementary Figures with legends Supplementary Tables S2, S4, S5-7

Differentially expressed pathways comparing transcriptomes in KRAS-TP53 co-altered (n=23) and KRAS-altered/TP53WT (n=5) derived from Cancer Cell Line Encyclopedia

Co-occupied and unique target genes shared between Creb and RNApol-II in chromatin immunoprecipitation and sequencing (ChIP-seq) experiments performed in murine Kras-Trp53 cooperative KPC pancreatic cancer cells

Accumulating real-world (RW) evidence of axicabtagene ciloleucel (axi-cel) has demonstrated comparable performance to that of pivotal trials. However, ∼57% of patients eventually relapse, with most requiring additional therapies. Being able to identify patients with risk of early relapse enables clinicians to consider additional interventions to extend survival outcomes. This study aimed to first comprehensively evaluate the RW performance of axi-cel in the multicenter University of California Health Systems using automated computational approaches. Second, we developed a decision tree machine learning (ML) model to identify patients with risks of early relapse within 6 months. A total of 416 adult patients with diffuse large B-cell lymphoma (DLBCL) receiving axi-cel between 2017 and 2024 were included in the study. The median progression-free survival (PFS) and overall survival (OS) were 10.1 and 54.4 months; the 18-month PFS and OS rates were 41.6% and 65.5%, respectively. Severe CRS and ICANS were observed in 18.8% and 32.5% of patients. The ML model, relying on age and 6 routinely measured laboratory tests (lactate dehydrogenase, C-reactive protein, ferritin, hematocrit, platelet count, and prothrombin time), achieved a high area under the receiver operating characteristic curve score of 0.82. The decision curve analysis indicated positive net benefit of the model across a broad range (0-0.7) of decision thresholds, suggesting clinical utility in diverse scenarios. This study further confirmed the RW performance of axi-cel in diverse populations. Our ML model represented a novel approach to identify patients that may benefit from additional interventions to extend survival outcomes. Following prospective confirmation study, our model and decision tree approach may support clinical decision making in patients with high-risk DLBCL.

Tumor-infiltrating lymphocyte (TIL) therapy is a type of personalized immunotherapy that harnesses the antitumor activity of endogenous immune cells. While TIL therapy has been in clinical investigation since the 1980s and shown promising signs of clinical activity in immunogenic solid tumors such as melanoma, more recent improvements in product manufacturing and characterization have demonstrated consistent efficacy and the feasibility of administering TIL therapy on a larger scale. Lifileucel was granted accelerated approval by the US Food and Drug Administration in February 2024 for the treatment of advanced melanoma, marking the first regulatory approval of a TIL product, and also the first approval of cellular therapy for the treatment of any solid tumor. Despite this landmark event, questions remain surrounding optimal TIL timing, sequencing with other treatment modalities, and the optimal TIL repertoire and phenotype. Innovations in cellular engineering are expected to improve the antitumor efficacy and safety profile of TIL therapy, advance our understanding of how best to deliver TIL therapy, and provide hope for paradigm-shifting approaches in the treatment of advanced melanoma as well as for other solid tumors.

Background: Allogeneic hematopoietic stem cell transplantation (allo-SCT) is an effective treatment for various hematologic cancers, though it often results in severe side effects and psychological distress, which can negatively impact health outcomes. Integrative therapies like mindfulness-based stress reduction (MBSR), mindfulness meditation (MM), and music therapy (MT) yield promising results in enhancing both psychosocial outcomes (eg, reducing anxiety and depression) and physiological adaptation (eg, decreasing inflammation) in cancer patients. Objective: We developed and refined, using focus groups and environmental and field testing, an eHealth-delivered mindfulness-based music therapy (eMBMT) intervention aimed at improving health-related quality of life, symptom burden (ie, pain, fatigue, and sleep), disease activity (ie, chronic graft-versus-host disease, cytomegalovirus activation, and infections) and psychosocial (ie, depression, anxiety, and cancer-specific distress) and physiological adaptation (ie, inflammation and immune reconstitution) tailored to adults receiving allo-SCT. Methods: eMBMT intervention content is grounded in MT, MM, and MBSR, developed by a multidisciplinary team, and adapted for adults undergoing allo-SCT. eMBMT content was refined through focus groups and usability and field testing. Focus groups used a semistructured interview guide, while field testing used the “think aloud” method. Usability was evaluated using the 30-item Usefulness, Satisfaction, and Ease of Use (USE) questionnaire. Descriptive statistics analyzed the USE questionnaire and participant characteristics, while rapid qualitative analysis was applied to focus groups and field-testing sessions. Survivors eligible to participate in the focus groups and usability and field testing were adults (>18 years old) who received an allo-SCT (<36 months) for myelodysplastic syndrome, acute myeloid leukemia, or chronic myeloid leukemia, and were in remission for greater than 3 months. Results: During the focus groups, participants (n=11; mean age 43.6, SD 17.8 years) provided qualitative feedback highlighting the shock of diagnosis, challenges during hospitalization, and coping strategies posttreatment. The eMBMT platform received positive evaluations for usefulness (mean 6.47, SD 0.29), ease of use (mean 6.92, SD 0.60), and satisfaction (mean 6.16, SD 0.82). Key themes from field testing highlighted the significance of social support, hope, and maintaining an active lifestyle. Suggestions for improvement included incorporating more representative content, reducing text, enhancing guidance, offering diverse music options, and streamlining blood sample collection. Conclusions: The eMBMT intervention is a comprehensive, user-friendly eHealth tool tailored to the unique needs of allo-SCT patients. The positive feedback and identified areas for improvement underscore its potential to enhance well-being, symptom management, and overall quality of life for cancer survivors. A future pilot randomized controlled trial will further evaluate the feasibility, acceptability, and preliminary efficacy of the eMBMT intervention in improving health-related quality of life, symptom burden, disease activity, and psychosocial and physiological adaptation.

Supplementary Methods Supplementary Figures with legends Supplementary Tables S2, S4, S5-7