Low subcutaneous adipose tissue and myosteatosis are prognostic factors after allogeneic hematopoietic stem cell transplantation.

OBJECTIVE: Allogeneic hematopoietic stem cell transplantation (allo-HSCT) represents the only curative treatment option for several hematological neoplasms. This study aimed to assess the parameters of body composition as predictors of post-transplant overall survival (OS) and adverse events in patients with leukemia, myelodysplastic syndromes (MDS), and myeloproliferative neoplasms (MPN). METHODS: This was a retrospective study of 122 adult patients who underwent their first allo-HSCT. The CT-based semi-automated measurement of subcutaneous adipose tissue (SAT), visceral adipose tissue (VAT), visceral-to-subcutaneous fat ratio (VSR), sarcopenia in terms of skeletal muscle index (SMI), and myosteatosis based on the skeletal muscle radiation attenuation (SM-RA) was performed. Cox regression analysis was used to assess the association of body composition parameters with OS. RESULTS: In the univariate analysis, low SAT and myosteatosis were associated with lower OS (hazard ratio [HR] 2.02, 95% confidence interval [CI] 1.16-3.51, p = 0.01) and (HR 2.50, 95% CI 1.48-4.25, p =< 0.001), respectively. This association remained significant after adjusting for relevant covariates, with HR 2.32, 95% CI 1.23-4.38, p = 0.01 and HR 2.86, 95% CI 1.51-5.43, p =< 0.001, respectively. On the contrary, VAT, VSR, sarcopenia, and sarcopenic obesity were not statistically significant in OS. Severe post-transplant adverse events were more common in the low SAT group (odds ratio [OR] 3.12, 95% CI 1.32-7.40, p = 0.01) and OR 3.17, 95% CI 1.31-7.70, p =< 0.01 in the age- and sex-adjusted analysis. CONCLUSION: Low SAT and myosteatosis may contribute to an increased risk of post-transplant mortality, while low SAT appears to increase the risk of severe post-transplant adverse events.

Parameters of body composition do not predict survival in patients with multiple myeloma undergoing autologous stem cell transplantation.

Studies regarding the influence of body composition parameters as predictors on overall survival (OS) in patients with multiple myeloma (MM) are scarce. OS and progression-free survival (PFS) were retrospectively assessed in 129 patients with MM undergoing autologous stem cell transplantation (ASCT) after a follow-up of 2 years. A computed tomography (CT) based semi-automated assessment of body composition was performed. No statistically significant differences were noted in 2-year OS, PFS, or post-transplant adverse events in the body composition groups of subcutaneous adipose tissue (SAT) (low vs. high-SAT), visceral adipose tissue (VAT) (low vs. high-VAT), visceral-to-subcutaneous fat ratio (VSR) (low vs. high VSR), and sarcopenia in terms of skeletal muscle index (SMI) (non-sarcopenic vs. sarcopenic). In conclusion, adipose and muscle tissue do not limit OS or affect the PFS in patients with MM undergoing ASCT.

Tislelizumab plus zanubrutinib for Richter transformation: the phase 2 RT1 trial.

In patients with chronic lymphocytic leukemia, Richter transformation (RT) reflects the development of an aggressive lymphoma that is associated with poor response to chemotherapy and short survival. We initiated an international, investigator-initiated, prospective, open-label phase 2 study in which patients with RT received a combination of the PD-1 inhibitor tislelizumab plus the BTK inhibitor zanubrutinib for 12 cycles. Patients responding to treatment underwent maintenance treatment with both agents. The primary end point was overall response rate after six cycles. Of 59 enrolled patients, 48 patients received at least two cycles of treatment and comprised the analysis population according to the study protocol. The median observation time was 13.9 months, the median age was 67 (range 45-82) years. Ten patients (20.8%) had received previous RT-directed therapy. In total, 28 out of 48 patients responded to induction therapy with an overall response rate of 58.3% (95% confidence interval (CI) 43.2-72.4), including 9 (18.8%) complete reponse and 19 (39.6%) partial response, meeting the study's primary end point by rejecting the predefined null hypothesis of 40% (P = 0.008). Secondary end points included duration of response, progression-free survival and overall survival. The median duration of response was not reached, the median progression-free survival was 10.0 months (95% CI 3.8-16.3). Median overall survival was not reached with a 12-month overall survival rate of 74.7% (95% CI 58.4-91.0). The most common adverse events were infections (18.0%), gastrointestinal disorders (13.0%) and hematological toxicities (11.4%). These data suggest that combined checkpoint and BTK inhibition by tislelizumab plus zanubrutinib is an effective and well-tolerated treatment strategy for patients with RT. ClinicalTrials.gov Identifier: NCT04271956 .

Low skeletal muscle mass is a predictor of treatment related toxicity in oncologic patients. A meta-analysis.

BACKGROUND & AIMS: The purpose of this meta-analysis was to summarize the published data regarding associations between occurrence of severe treatment related toxicity and low skeletal muscle mass (LSMM) in oncologic patients and to perform a meta-analysis based on a large sample. METHODS: MEDLINE, Cochrane, and SCOPUS databases were screened for associations between LSMM and treatment related toxicity in oncologic patients up to June 2021. Overall, 48 studies met the inclusion criteria. The following data were extracted: authors, year of publication, study design, number of patients, influence of LSMM on treatment toxicity (odds ratios and confidence intervals). The methodological quality of the involved studies was checked according to the QUADAS instrument. The meta-analysis was undertaken by using RevMan 5.4 software. DerSimonian and Laird random-effects models with inverse-variance weights were used to account for the heterogeneity between the studies. RESULTS: The included 48 studies comprised 4803 patients with different malignant diseases. LSMM occurred in 1966 patients (40.9%). LSMM was associated with therapy toxicity (simple logistic regression) with an odds ratio OR = 2.19, CI95%= (1.78-2.68). LSMM was associated with DLT in patients underwent curative treatment (16 studies, 2381 patients) with OR = 2.48, CI95%= (1.77-3.48). LSMM predicted DLT in patients underwent palliative chemotherapy (30 studies, 2337 patients)with OR = 2.06, CI95%= (1.56-2.74). In the subgroups received different palliative therapies, relationships between LSMM and DLT were as follows: conventional chemotherapies (7 studies, 600 patients) OR = 2.14, CI95%= (1.38-3.31); different kinases inhibitors (13 studies, 906 patients) OR = 3.08, CI95%= (1.87-5.09); checkpoint inhibitors (7 studies, 557 patients) OR = 1.30, CI95%= (0.79-2.11). CONCLUSIONS: LSMM is an essential factor of treatment toxicity in oncologic patients. Association between LSMM and DLT is strongest in patients received therapy with kinases inhibitors. The influence of LSMM on DLT is lowest in patients underwent treatment with checkpoint inhibitors. The presence of LSMM should be included into radiological reports and provided to oncologists to optimize chemotherapy. LSMM should be included into dose calculation for chemotherapy.