ALBERT

Description: Background: Taste disturbance, or dysgeusia, negatively affects quality of life and may lead to poorer nutritional status after high-dose melphalan and autologous stem cell transplantation (mel-AHCT) for patients with multiple myeloma (MM). Despite its frequency, dysgeusia has received limited prospective study. Here, we report the interim results of an on-going prospective clinical trial aimed at evaluating the feasibility of performing chemical gustometry, and quantifying the effects of dysgeusia on patient-reported symptom burden and nutritional status in MM patients undergoing mel-ASCT. We also sought to identify novel associations between mel serum and salivary pharmacokinetic (PK) levels and dysgeusia. Methods: For this study, chemical gustometry was considered feasible for use as an endpoint in a future clinical trial if 〉 60% of the patients could complete 〉 60% of the evaluations. Chemical gustometry was performed according to the Henkin method (Henkin et al., Am J Otolaryngol 2013) at baseline (pre-AHCT) and on days -1, +7, +14, and +30 to test the 5 basic flavors: sweet (sucrose), sour (citric acid), salty (sodium chloride), bitter (quinine), and umami (monosodium glutamate). These data were used to calculate a total gustometry score (maximum value of 30). At the above time-points as well as day +3 and +10, caloric intake (kcal) was calculated using the USDA 5-Step Multiple-Pass Approach with 24-hour recall, and patient-reported symptom burden was assessed using the MD Anderson Symptom Inventory-Myeloma Module (MDASI-MM). Serum PK levels were drawn at 6 times points after mel infusion to calculate an area under the curve (AUC). Spearman rank-sum correlation was calculated for serum mel AUC and its association with total gustometry scores, caloric intake, and MDASI scores over time using a scaled 30-day AUC. A peak salivary mel level was measured at 75 minutes after infusion, and correlated with total gustometry scores, caloric intake, and MDASI scores. Results: To date, 22 patients with MM undergoing mel-AHCT have been enrolled and have follow-up data through day +30. Eighteen patients (82%) completed 〉 60% of all assessments. Median age was 62 (41-75), and 11 (50%) were female. Nineteen (86%) patients received mel 200 mg/m2 and 3 (14%) received mel 140 mg/m2. Median serum mel AUC was 12.6 mg*h/L (range 5.8-17.5), and median salivary mel was 119 ng/ml (range 25-662). Higher serum mel AUC correlated with higher salivary mel levels [Spearman correlation 0.59, p=0.004] as shown in Figure 1. Higher serum mel AUC was associated with poorer caloric intake from pre-ASCT to day +30 [Spearman correlation -0.45, p=0.04] as shown in Figure 2. Higher serum melphalan AUC was also associated with higher total MDASI scores (worse symptom burden) from pre-ASCT to day +30 [Spearman correlation 0.57, p=0.005], but was not significantly associated with total gustometry scores. A higher peak salivary mel level was associated poorer caloric intake from pre-ASCT to day +30 [Spearman correlation -0.49, p=0.02]. Among all patients, MDASI scores appeared highest on day +10, and total gustometry scores and caloric intake appeared lowest on days +7 and +10, respectively. At days +7, +14, and +30, 9 of 16 patients (56%), 8 of 17 patients (47%), and 9 of 19 (47%) had a drop of at least 1 point in gustometry score compared to baseline, respectively. Overall, gustometry scores appeared to improve by day +30, but often did not return to baseline (Figure 3A-C). Conclusion: Chemical gustometry is feasible and comprehensively evaluates changes in taste function in MM patients after AHCT. The lowest gustometry scores were apparent on day +7 and often did not return to baseline by day +30, confirming the persistence of dysgeusia after AHCT. Moreover, higher serum and salivary mel levels are associated with poorer caloric intake and higher symptom burden scores within the first 30 days after AHCT. Preventing mel overexposure by targeted mel PK dosing may reduce dysgeusia, improve caloric intake, and limit symptom burden in MM patients after AHCT. Disclosures Shah: Janssen: Research Funding; Amgen: Research Funding. Peled:Seres Therapeutics: Research Funding.

Description: Background: CAR T therapy is FDA approved for specific relapsed/ refractory (R/R) B cell lymphomas and acute lymphoblastic leukemia (ALL), and clinical trials are ongoing for R/R multiple myeloma (MM). Cytopenias have been observed post-CAR T, yet there is minimal data delineating the pathobiology and trends. We report the largest series to our knowledge thus far, of hematological recovery and factors affecting count recovery after CAR T. Methods: We retrospectively reviewed adult patients who received CAR T for R/R B cell lymphomas after FDA approval and those treated for R/R B cell ALL (NCT01044069) and MM (NCT03070327) at our center. Blood counts were collected for up to 12 months or until censored for relapse, progression or initiation of chemotherapy/ conditioning for autologous or allogeneic stem cell transplantation (HCT)/ subsequent treatment with CAR T. Only patients with follow-up 〉 30 days were included. "Recovery" for the respective blood count was defined as hemoglobin 〉 8g/dL and platelets 〉 50,000/µL without transfusion support in 2 weeks and 1 week, respectively; absolute neutrophil count (ANC) 〉 1,000/µL and white cell count (WBC) 〉 3,000/µL without growth factor support in 2 weeks. "Normalization" was defined as normal range for the laboratory; hemoglobin 〉 11.2g/dL in women and 12.5g/dL in men, platelets 〉 160,000/µL, ANC 〉 1,500/µL and WBC 〉 3,000/µL without transfusion support as above. "Complete count recovery" refers to recovery per above criteria in all 4 counts. Categorical variables were compared using Fisher's exact test and continuous variables using the Wilcoxon rank-sum test. Results: Eighty three patients were included (Table 1). Using the noted nadir values, grade 1-2 and 3-4 anemia was seen in 22% and 78%, thrombocytopenia in 29% and 66%, neutropenia in 3% and 96% while leucopenia in 0% and 100%, respectively. During the follow-up, 66% patients received packed red cell transfusion, 52% received platelet transfusion and 62% received growth factor support. By 1 month (n=83), recovery of hemoglobin, platelets, ANC and WBC was noted in 61%, 51%, 33% and 28%, respectively. At 3 months (n=41), these respective percentages were 93%, 90%, 81% and 59%. All patients had recovered hemoglobin and platelet count by 4 months (n=17), and ANC by 9 months (n=14). By 3 months, normalization of hemoglobin, platelets, ANC and WBC was noted in 39%, 34%, 71%, and 39%, respectively. Upon examination of potential variables in a univariate model, lack of recovery of hemoglobin, platelets, ANC and complete counts recovery at 1 month was statistically significantly associated with type of CAR construct, higher grade (grade 3-4 vs grade 1-2 vs none) cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) as well as a higher peak CRP and ferritin (data for complete count recovery in Table 2). Additionally, lack of hemoglobin recovery at 1 month was associated with lymphodepletion using high dose cyclophosphamide (recovered vs no recovery in 58% vs 42%, p=0.01) and diagnosis of ALL (65% vs 35%, p = 3 prior lines of therapy (78% vs 22%, p = 0.04). At 3 months, absence of complete count recovery was associated only with the CAR T construct utilized. A multivariate logistic regression model resulted in wide confidence intervals due to small size of subgroups, hence leading to unreliable point estimates (data not shown). Conclusions: Our study shows that blood counts recover in most patients who have not progressed or received additional therapy by 3 months post-CAR T. The association of count recovery with severity of CRS, ICANS as well as inflammatory marker levels indicates that inflammatory response post-CAR T influences hematological recovery in these patients. The association of count recovery and CAR construct can be influenced by underlying diagnosis as specific CAR constructs were used for specific diagnosis. Since patients with no disease response were excluded and were censored at progression, these effects are less likely to be affected by disease response; however the association of depth of response could not be evaluated in this study. These results warrant future studies to understand underlying mechanisms of inadequate recovery. Disclosures Scordo: McKinsey & Company: Consultancy; Angiocrine Bioscience, Inc.: Consultancy. Sauter:Kite/Gilead: Consultancy; Precision Biosciences: Consultancy; Genmab: Consultancy; Celgene: Consultancy; GSK: Consultancy; Juno Therapeutics: Consultancy, Research Funding; Sanofi-Genzyme: Consultancy, Research Funding; Spectrum Pharmaceuticals: Consultancy; Novartis: Consultancy. Santomasso:Novartis: Consultancy; Kite/Gilead: Consultancy; Juno/Celgene: Consultancy. Palomba:Noble Insights: Consultancy; Hemedicus: Other: Immediate Family Member, Speakers Bureau ; Evelo: Other: Immediate family member, Equity Ownership; MSK (IP for Juno and Seres): Other: Immediate Family Member, Patents & Royalties - describe: intellectual property rights ; Kite Pharmaceuticals: Other: Immediate Family Member, Membership on an entity's Board of Directors or advisory committees; Merck & Co Inc.: Other: Immediate Family Member, Consultancy (includes expert testimony); Seres Therapeutics: Other: Immediate Family Member, Equity Ownership and Membership on an entity's Board of Directors or advisory committees; STRAXIMM: Other: Immediate Family Member, Membership on an entity's Board of Directors or advisory committees; Pharmacyclics: Membership on an entity's Board of Directors or advisory committees. Shah:Amgen: Research Funding; Janssen: Research Funding. Batlevi:Juno Therapeutics: Consultancy, Membership on an entity's Board of Directors or advisory committees. Smith:Celgene: Consultancy, Patents & Royalties, Research Funding; Fate Therapeutics and Precision Biosciences: Consultancy. Giralt:Celgene: Consultancy, Research Funding; Takeda: Consultancy; Sanofi: Consultancy, Research Funding; Amgen: Consultancy, Research Funding. Brentjens:Celgene: Consultancy; JUNO Therapeutics: Consultancy, Patents & Royalties, Research Funding. Park:Takeda: Consultancy; Novartis: Consultancy; Kite Pharma: Consultancy; Incyte: Consultancy; Allogene: Consultancy; Amgen: Consultancy; AstraZeneca: Consultancy; Autolus: Consultancy; GSK: Consultancy. Perales:Bristol-Meyers Squibb: Honoraria, Membership on an entity's Board of Directors or advisory committees; Incyte: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Nektar Therapeutics: Honoraria, Membership on an entity's Board of Directors or advisory committees; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees; Omeros: Honoraria, Membership on an entity's Board of Directors or advisory committees; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees; Merck: Consultancy, Honoraria; Medigene: Membership on an entity's Board of Directors or advisory committees; Servier: Membership on an entity's Board of Directors or advisory committees; Kyte/Gilead: Research Funding; Miltenyi: Research Funding; MolMed: Membership on an entity's Board of Directors or advisory committees; NexImmune: Membership on an entity's Board of Directors or advisory committees; Abbvie: Honoraria, Membership on an entity's Board of Directors or advisory committees; Bellicum: Honoraria, Membership on an entity's Board of Directors or advisory committees. Mailankody:Celgene: Research Funding; Juno: Research Funding; Janssen: Research Funding; Takeda Oncology: Research Funding; CME activity by Physician Education Resource: Honoraria.

Description: Background: High-dose melphalan with autologous stem cell transplantation (AHCT) is a key component in the treatment of patients with multiple myeloma (MM). The use of AHCT has been shown in several clinical trials to improve event-free and overall survival and is accepted as standard of care in medically fit patients. The use of high doses of melphalan is associated with a period of myelosuppression which has not been reduced despite higher doses of infused stem cells and stem cell fractionation. This period of obligate neutropenia results in significant life-threatening complications and increased financial costs. The aim of this study was to identify predictors of duration of neutropenia as a baseline to developing strategies that minimize neutropenia and thereby symptom burden after high-dose chemotherapy and AHCT. Methods: We retrospectively reviewed patients who had a diagnosis of MM and who had a first AHCT at our Institution between 1/2011 and 12/2016 with high-dose melphalan. We determined the incidence of absolute neutropenia (defined as ANC