Teclistamab is a BCMA/ CD3 bispecific T cell engager, FDA approved in relapsed/refractory multiple myeloma (RRMM) after 4 prior lines of therapy, based on the results of MajesTEC-1 study. Early ...toxicities of teclistamab include CRS and ICANS. To mitigate the risk of CRS/ICANS, teclistamab is administered in a step-up dosing approach. 48h inpatient observation after each of the 3 step-up doses is recommended, although not mandated by FDA. Based on our outpatient CAR-T program experience, we implemented an outpatient teclistamab step-up dosing administration program.
To evaluate safety of outpatient teclistamab administration.
Retrospective review of toxicity outcomes of patients treated in outpatient teclistamab program at Fox Chase.
Comprehensive Cancer Center, BMT program.
Eligible patients were required to stay within 1h from Fox Chase with a caregiver during the observation period (days 1-10). Patients and caregivers received education on CRS and ICANS. Teclistamab was administered on days 1, 3, and 8. Safety monitoring protocol included daily evaluation in the outpatient clinic, home monitoring of vital signs, and 8 pm physician phone call on days 1-5 and 8-10, within 48h window after each step-up dose. CBC, CMP, CRP, ferritin were monitored at each visit. Patients with CRS/ ICANS of any grade were admitted for observation and management.
Between 12/2022-5/2023, 18 patients completed outpatient teclistamab step-up dosing. The median age was 66y (46-81). 12(66.7%) patients did not have CRS/ICANS. 5(27.8%) patients had grade 1 CRS, of which 1(5.6%) had concurrent grade 1 ICANS. 1(5.6%) patient had grade 2 CRS. Of the 6 CRS events, 3(50%) occurred after the first dose and 3(50%) after the second dose. 5 of 6 patients with CRS received 1 dose of tocilizumab, and the patient with concurrent ICANS also received dexamethasone, with prompt resolution of symptoms. All patients completed step-up dosing with no recurrent CRS/ICANS.
Outpatient teclistamab step-up dosing administration with close monitoring and prompt hospitalization for toxicity management is safe and feasible in heavily pre-treated RRMM patients. This approach allows a significant reduction of inpatient stay, resulting in significant healthcare resource savings and improvement of patients’ experience.
Abstract Introduction: Molecular minimal residual disease (MRD) status correlates with disease relapse in patients (pts) with diffuse large B cell lymphoma (DLBCL). However, the clinical impact of ...early treatment intervention a time of detectable MRD (dMRD) prior to clinical relapse is unknown. Checkpoint inhibitor (CPI) therapy has activity in some pts with DLBCL. We hypothesized that early CPI therapy in patients with dMRD without clinical relapse may lower relapse rate. We conducted a pilot study in high risk pts in remission after most recent line of therapy (LOT) in whom maintenance nivolumab (MN) was offered at time of dMRD to assess effect on MRD clearance and relapse rate. Methods: Pts >18 years (yrs) with high-risk DLBCL (ABC-subtype, high grade B cell lymphoma (HGBCL), MYC translocation, relapsed/refractory disease, or Ki67 >90%) who had achieved CR on most recent LOT were eligible. Patients were monitored for detectable MRD (dMRD) based on the clonoSEQ assay for circulating tumor DNA (ctDNA). Pts had monthly MRD assessment and every 4 month imaging for 2 yrs. If conversion from uMRD to dMRD without clinical relapse, pts received MN (240 mg IV q2 weeks) for up 2 yrs. Pts with overt relapse at time of dMRD or dMRD at initial MRD assessment were ineligible for MN. The primary endpoint was rate of conversion from dMRD to undetectable MRD (uMRD). Results: 20 pts were screened and 15 pts enrolled between June 2018 and March 2022. 4 had transformed DLBCL (2 from FL, 1 from MZL, and 1 Richter’s transformation from CLL), 2 pts had HGBCL (one of which was also transformed). All pts with dMRD had radiographic relapse within 4 months of molecular relapse. No pts with uMRD by ctDNA had clinical relapse on study during 2 yrs follow up. Of the 8 pts who enrolled after first LOT, none had molecular or clinical relapse. Of the 7 pts with 2+ prior LOT, 3 had dMRD: two had clinical relapse at same time as dMRD and were taken off study (one had dMRD at baseline MRD assessment and the other 135 days post enrollment after initial period of uMRD). In the single patient eligible for MN, dMRD preceded radiographic relapse by 105 days, 410 days after enrollment. The pt received 2 cycles of MN before clinical progression and was taken off study. This pt failed to achieve conversion of dMRD to uMRD. Conclusion: Due to small sample size and lower than expected relapse, we were unable to demonstrate conversion of dMRD to uMRD using MN. However, this pilot study did confirm high correlation of uMRD and dMRD status with disease free survival and clinical relapse within 4 months, respectively. If strong negative predictive value is confirmed in a larger study, ctDNA MRD testing may be used to spare pts from imaging or to guide additional work up in pts with inconclusive findings on scans. Citation Format: Shazia Nakhoda, Tamarrah Sklarz, Cheyenne Pagan, Matthew Matasar, Zachary A. Frosch, Marcus Messmer, Asya Varshavsky Yanovsky, Rashmi Khanal, Carlyn Tan, Eli Mikkelsen, Henry Fung, Eric Ross, Mark Roschewski, Allison Jacob, Nadia Khan. Circulating tumor DNA and nivolumab maintenance: A pilot study in diffuse large B cell lymphoma abstract. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(7_Suppl):Abstract nr CT245.
Introduction Induction chemotherapy (IC) in acute myeloid leukemia (AML) in younger and fit patients has historically combined an anthracycline (ie, daunorubicin or idarubicin) with the ...antimetabolite cytarabine, which has been termed the 7 + 3 regimen. Response rates with this current standard approach show complete response rates of 70-80%, however 30-40% still eventually relapse. Recently, the MD-Anderson group published a phase II study in which the drug venetoclax was added to the standard anthracycline/cytarabine induction regimen of FLAG-IDA. Results from this study showed an impressive 96% response rate for newly diagnosed (ND) AML patients. Based on these results we began to adopt this approach for our patients. We have induced 21 patients with this approach at our institution and have had comparable results. No study has compared outcomes between this approach and that of standard 7 +3 in regards to response rates. Based on our improved outcomes we compared outcomes between these two approaches in our patient population by doing a retrospective chart based review on all patients that received cytotoxic induction treatment for ND-AML between 2000-2023. Methods Patients between 2020-2023 that were treated with induction cytotoxic chemotherapy for AML, based on WHO 2016 criteria, were retrospectively reviewed. Patients either received 7+3 or 7+3 plus midostaurin if they were FLT3+ in one arm or FLAG-IDA/Venetoclax. Patients received FLAG-IDA/Venetoclax regardless of FLT3+ status or risk of disease. Patients with extra medullary disease were excluded from this review as well as patients that received an IDH1 or 2 inhibitors in combination with 7 +3. Results Overall 39 patients were included in this study, 20 patients in the FLAG-IDA/Venetoclax arm and 19 patients in the 7/3 arm. In patients which response was able to be evaluated patients in the FLAG-IDA/Venetoclax cohort had a 100% overall response rate with a 95% (N = 19/20) complete response rate. Patients in the 7/3 cohort the complete remission rates were 66% (N = 12/16) with 3 of the patients achieving a complete remission with re-induction. Sixty-day morality rate was 5% (N = 1/20) in patients receiving FLAG-IDA/Venetoclax compared to 16% (N = 3/19). In terms of neutrophil recovery and toxicity results were comparable in both arms, with the average day to cell recovery being the similar in both groups. Conclusions FLAG-IDA/Venetoclax compared to standard 7/3 +/- FLT3 directed therapy in our patient population resulted in improved response rates and decreased 60-day mortality. Our results are similar to previously published reports in patents with ND-AML. Toxicity profiles were similar with the clear benefit of decreased early morality are increased response rates.
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Background: Allogeneic stem cell transplant (allo SCT) is a potentially curative therapy for hematological malignancies but is associated with high treatment related non-relapse mortality ...(NRM). Post-transplant care requires large amount of healthcare and patient resources, imposing higher burden on patients with lower socio-economic status (SES). Adverse health outcomes have been noted in males from lower SES background. We analyzed the effects of social factors on post-transplant survival and NRM in the diverse patient population treated at our institution. Methods: We retrospectively reviewed patients who underwent allo SCT at our program in 2015-2021. We collected baseline patient (demographics, KPS, HCT-CI), disease (diagnosis, risk index) and transplant characteristics (donor type, conditioning intensity). We extracted neighborhood level income data from US Census. Primary outcomes were survival and NRM. We used Fisher’s Exact, Wilcoxon Ranksum tests and logistic regressions. Results: 210 patients (116 males and 94 females) were included in the analysis. Neighborhood level estimated household income range was $26,041-163,074. Both 1 year OS and NRM, but not 100 days OS, significantly correlated with income. Patients who were alive at 1 year follow up (74.8% pts) had median income of $72K, compared to $62K for patients who died before 1 year (25.2% pts) and 60.5K for patients who died before 1 year without disease progression (13.3% pts) (p 0.032). The effect of income on NRM remained significant on multivariable analysis, adjusted for year of transplant, age, race, ethnicity, donor type, KPS, comorbidity index, regimen intensity, and disease risk. Increased conditioning intensity and haplo donor were also associated with increased 1 year NRM, while race and ethnicity did not have significant effect on 1 year NRM on multivariable analysis. The effect of income on NRM was dramatically different in male vs female patients. In men, a $10K increase in neighborhood income reduced the odds of NRM substantially (OR = 0.46, 95% CI 0.28-0.75), while in women there was no effect (OR 1.02, 95% CI 0.71-1.45). 1 year NRM in men was 9% vs 24% for higher vs lower neighborhood income (p 0.036), and in women 8% vs 13% (p 0.52). Conclusions: Our study identifies male patients residing in lower income neighborhoods as a subgroup at increased risk for NRM after allo SCT, after adjustment for the biological variables. The negative effects of lower neighborhood income and male gender become apparent with 1 year but not 100 days follow up, reflecting increasing difficulties with high resourses utilization over prolonged time period. Careful evaluation of controllable risk factors and optimizing social support may reduce the rate of complications. Further research into the factors mediating the relationship of neighborhood income with gender on survival and treatment-related mortality post allo SCT seems necessary.
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Background: Data from the ongoing phase 2 MagnetisMM-3 (NCT04649359) study demonstrated the efficacy and safety of elranatamab in patients (pts) with RRMM and no prior BCMA-directed therapy ...(Cohort A). Results in high-risk subgroups are reported. Methods: Eligibility criteria, dosing and administration were previously reported (Bahlis, ASH 2022). Subgroups analyzed were R-ISS stage (I/II/III ), cytogenetic abnormalities (standard/high risk high-risk defined by the presence of t(4;14), t(14;16) or del(17p)), extramedullary disease (EMD) at baseline (Y/N), bone marrow plasma cell involvement (BMPC) at baseline (<50%/≥50%), and penta-refractory disease (Y/N). Results include data up through ~12 months after last pt initial dose. Results: Median treatment durations and the proportions of pts receiving treatment at the data cut-off are reported in the Table. The most frequent cause of discontinuation was progressive disease which was higher for all high-risk subgroups than the corresponding lower risk subgroups. A clinical benefit, assessed by the objective response rate (ORR), was observed across subgroups (Table). A multivariable logistic regression analysis for ORR including baseline age, ECOG, sex, region, cytogenetic risk, presence of EMD, BMPC involvement, prior stem cell transplant, R-ISS stage, number of prior lines, type of myeloma, and penta-refractory disease showed presence of EMD at baseline and non-IgG myeloma (vs IgG) as predictive of lower ORR. Light chain-only myeloma (vs IgG) was predictive of higher ORR. Median duration of response (DOR) was not reached in subgroups by 12 months, DOR rate at 12 months is reported in the Table. Any grade TEAEs were reported in 100% of pts in the study. The incidence of grade 3/4 TEAEs was overall similar across subgroups (Table). Conclusions: Elranatamab is efficacious and has a manageable safety profile in pts with high-risk RRMM and no prior BCMA-directed therapy. Clinical trial information: NCT04649359 . Table: see text
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