- |||||||||| Poor Survival Outcomes of Checkpoint Inhibitors for B-Cell Lymphomas Relapsing after or Refractory to CAR T-Cell Therapy: A Real-World Cohort from 15 U.S. Academic Institutions (R02-R05 (Ernest N. Morial Convention Center)) - Nov 4, 2022 - Abstract #ASH2022ASH_3563;
Most patients received axicabtagene ciloleucel (53%), followed by tisagenlecleucel (26%) and lisocabtagene maraleucel (19%)...Most patients received pembrolizumab (49%), followed by nivolumab (43%), and 29% received concurrent therapies with CPI, mostly other immunotherapies and lenalidomide...Significant improvement in OS in patients receiving CPI concurrently with other therapies may warrant additional study to identify potential synergistic combinations. Finally, these data confirm the dismal prognosis of patients with refractory or early relapsing lymphoma after CAR-T and a pressing need for effective therapeutic approaches.
- |||||||||| Longitudinal Patient-Reported Outcomes in Patients Receiving Chimeric Antigen Receptor (CAR) T-Cell Therapy (Hall D (Ernest N. Morial Convention Center)) - Nov 4, 2022 - Abstract #ASH2022ASH_3176;
Patients receiving CAR T-cell therapy experience significant QOL impairment and physical and psychological symptom burden, which peaks 1 week after cell infusion and improves by 6 months post-infusion. Given high rates of persistent severe symptoms and clinically significant psychological distress, interventions to improve the QOL of these patients are warranted.
- |||||||||| Kineret (anakinra) / SOBI
Anakinra for Treatment and Prevention of CAR-T Neurotoxicity: A Systematic Review of Evidence to Inform SIE-GITMO-Sidem Guidelines (Hall D (Ernest N. Morial Convention Center)) - Nov 4, 2022 - Abstract #ASH2022ASH_3095;
Preliminary studies also tested an early adoption of Anakinra for the prevention of severe ICANS. The above systematic review confirms the need of randomized clinical trials to assess the effectiveness (grade 5 ICANS, duration of ICANS, steroid cumulative dose) of Anakinra in different patients subgroups, i.e. severe ICANS, steroid-refractory ICANS, ICANS with concurrent CRS, patients at high risk of developing ICANS (Rubin 2020).
- |||||||||| Breyanzi (lisocabtagene maraleucel) / BMS, Kymriah (tisagenlecleucel-T) / Novartis, Yescarta (axicabtagene ciloleucel) / Gilead
Predictors and Implications of Renal Injury in Large Cell Lymphoma Patients Receiving CD19 CAR T Cell Therapy (Hall D (Ernest N. Morial Convention Center)) - Nov 4, 2022 - Abstract #ASH2022ASH_2906;
The association between renal injury and subsequent mortality suggests that AKI is a clinically and prognostically significant complication. The discovery that readily available biomarkers reflecting physiological reserve, disease burden, and systemic inflammation inform on renal injury risk may support personalized stratification for risk mitigation.
- |||||||||| Breyanzi (lisocabtagene maraleucel) / BMS, Kymriah (tisagenlecleucel-T) / Novartis, Yescarta (axicabtagene ciloleucel) / Gilead
Lymphodepleting Chemotherapy before CD19 Directed CAR T-Cell Therapy: Are 3 Days Necessary? (Hall D (Ernest N. Morial Convention Center)) - Nov 4, 2022 - Abstract #ASH2022ASH_2517;
Most lymphodepleting regimens use a combination of fludarabine and cyclophosphamide (flu/cy) but there is variability between dosing and duration of therapy...Of the patients that received 3 days of LD chemo, 54.8% (n=17) were treated with axicabtagene ciloleucel (axi-cel), 11 were treated with tisagenlecleucel (tisa-cel), and 3 received lisocabtagene maraleucel (liso-cel)...In this small patient sample, there were no significant differences in CAR T-cell efficacy or toxicity with a 2-day regimen. There is need for further prospective trials to ensure appropriate dosing of chemotherapy to optimize CAR T-cell response while minimizing toxicity.
- |||||||||| PIT565 / Novartis
PIT565, a First-in-Class Anti-CD19, Anti-CD3, Anti-CD2 Trispecific Antibody for the Treatment of B Cell Malignancies (Hall D (Ernest N. Morial Convention Center)) - Nov 4, 2022 - Abstract #ASH2022ASH_2197;
P1
Taken together, the findings from the preclinical studies suggest that PIT565 may achieve deeper and more durable responses compared to competitor CD3 bispecifics. First-in-human trial of PIT565 (NCT05397496) has been initiated and will be conducted in patients who are diagnosed with relapsed and/or refractory adult NHL after receiving two or more lines of chemotherapy and patients with relapsed and/or refractory B-ALL.
- |||||||||| Breyanzi (lisocabtagene maraleucel) / BMS, Kymriah (tisagenlecleucel-T) / Novartis, Yescarta (axicabtagene ciloleucel) / Gilead
Inflammatory Biomarker Clusters Are Predictive of Response and Toxicity in Large B-Cell Lymphoma Treated with CD19 CAR-T Cell Therapy (La Nouvelle Orleans Ballroom AB (Ernest N. Morial Convention Center)) - Nov 4, 2022 - Abstract #ASH2022ASH_1664;
These clusters could guide decision-making regarding hospitalization after CAR-T infusion and to preempt early inflammation and disease relapse in high-risk subgroups. Finally, to improve accessibility to cluster assignment, we developed a prediction model for cluster type based on readily available pre-lymphodepletion data and applied it towards an external center cohort as a proof-of-principle.
- |||||||||| Breyanzi (lisocabtagene maraleucel) / BMS, Kymriah (tisagenlecleucel-T) / Novartis, Yescarta (axicabtagene ciloleucel) / Gilead
CD19 CAR-T Outcomes in Patients with EBV-Positive DLBCL (Hall D (Ernest N. Morial Convention Center)) - Nov 4, 2022 - Abstract #ASH2022ASH_2507;
In the EBV + cohort, the median age was 47 years (range, 20-81) and included 5 (55%) pts with DLBCL-NOS, 3 (30%) pts with transformed follicular lymphoma, and one (15%) pt with high-grade B-cell lymphoma. The median number of prior lines of therapy was 2 (range, 1-5).
- |||||||||| Breyanzi (lisocabtagene maraleucel) / BMS, Kymriah (tisagenlecleucel-T) / Novartis, Yescarta (axicabtagene ciloleucel) / Gilead
Double Hit/Double Expressor Lymphomas: A Multicenter Analysis of Survival Outcomes with CD19-Directed CAR T-Cell Therapy (New Orleans Theater C (Ernest N. Morial Convention Center)) - Nov 4, 2022 - Abstract #ASH2022ASH_1536;
This represents a major therapeutic advance for this high-risk population with historically poor survival when treated with chemotherapy and supports early use of CART for these pts in the relapsed setting. DHL pts progressing post-CART have a dismal mOS of 2.7 mon, reflecting the urgent need for effective therapies post-CART failure.
- |||||||||| Journal: New and emerging therapies for the treatment of relapsed/refractory diffuse large B-cell lymphoma. (Pubmed Central) - Nov 2, 2022
These agents include polatuzumab vedotin, tafasitamab, loncastuximab tesirine, selinexor, and anti-CD19 chimeric antigen receptor T-cell therapies such as axicabtagene ciloleucel, tisagenlecleucel, and lisocabtagene maraleucel. This review summarizes the pharmacology, efficacy, safety, dosing, and administration of new agents recently approved for the treatment of relapsed/refractory DLBCL.
- |||||||||| Breyanzi (lisocabtagene maraleucel) / BMS
CAR-T cell immunotherapy in non-Hodgkin's lymphomas: lisocabtagene maraleucel (RAFFAELLO ROOM) - Oct 29, 2022 - Abstract #SIE2022SIE_220;
This review summarizes the pharmacology, efficacy, safety, dosing, and administration of new agents recently approved for the treatment of relapsed/refractory DLBCL. Lunch Meeting Supported by BRISTOL MYERS SQUIBB
- |||||||||| Breyanzi (lisocabtagene maraleucel) / BMS, Kymriah (tisagenlecleucel-T) / Novartis, Yescarta (axicabtagene ciloleucel) / Gilead, Daiichi Sankyo
Journal, CAR T-Cell Therapy, Cytokine release syndrome: A Model to Estimate Cytokine Release Syndrome and Neurological Event Management Costs Associated With CAR T-Cell Therapy. (Pubmed Central) - Oct 23, 2022
Across the base case and scenario analysis, liso-cel had the lowest weighted average CRS and NE costs per treated patient compared with axi-cel and tisa-cel owing to lower incidence rates and symptom severity. These findings highlight the economic implications of differences in safety among CAR T-cell therapies.
- |||||||||| Breyanzi (lisocabtagene maraleucel) / BMS
Journal: New Approval for Drug Treating Large B-Cell Lymphoma. (Pubmed Central) - Oct 1, 2022
Recruiting --> Active, not recruiting | N=108 --> 62 The Food and Drug Administration has approved lisocabtagene maraleucel (Breyanzi) to treat large B-cell lymphoma in adults who relapsed or were refractory after first-line treatment.Lisocabtagene maraleucel continues to be prescribed under the Risk Evaluation and Mitigation Strategy due to the risk of fatal or potentially fatal cytokine release syndrome and neurologic toxicities.Nurses need to closely monitor patients for these and for other serious adverse effects for at least seven days after infusion of the drug.
- |||||||||| Breyanzi (lisocabtagene maraleucel) / BMS
Enrollment closed, Trial completion date, Trial primary completion date: Study Evaluating the Safety and Pharmacokinetics of JCAR017 in B-cell Non-Hodgkin Lymphoma (TRANSCEND-NHL-001) (clinicaltrials.gov) - Sep 30, 2022
P1, N=385, Active, not recruiting,
The Food and Drug Administration has approved lisocabtagene maraleucel (Breyanzi) to treat large B-cell lymphoma in adults who relapsed or were refractory after first-line treatment.Lisocabtagene maraleucel continues to be prescribed under the Risk Evaluation and Mitigation Strategy due to the risk of fatal or potentially fatal cytokine release syndrome and neurologic toxicities.Nurses need to closely monitor patients for these and for other serious adverse effects for at least seven days after infusion of the drug. Recruiting --> Active, not recruiting | Trial completion date: Dec 2022 --> May 2024 | Trial primary completion date: Dec 2022 --> May 2024
- |||||||||| Breyanzi (lisocabtagene maraleucel) / BMS, Kymriah (tisagenlecleucel-T) / Novartis, Yescarta (axicabtagene ciloleucel) / Gilead, Daiichi Sankyo
DEBATE: CAR T-Cell or Autologous Stem Cell Transplantation (ASCT) for Relapsed LBCLPro ASCT () - Sep 22, 2022 - Abstract #SOHO2022SOHO_392;
In addition to the above, with no clearly demonstrable OS benefi t in the studies it is largely unknown whether salvaging post-fl udarabine, post-CAR-induced cytopenic patients with platinum-containing regimens followed by successful hematopoietic progenitor cell collection and HDT-ASCT is a feasible possibility in the third line. Lastly, the fi nancial toxicity of CAR T therapy9 needs to be taken into consideration to the treatment calculus in 2L r/r LBCL.
- |||||||||| Novel Agents in Chronic Lymphocytic Leukemia (CLL) () - Sep 21, 2022 - Abstract #SOHO2022SOHO_373;
BH3-mimetics which target Bcl-xL, such as navitoclax, are not being developed in CLL due to concerns of thrombocytopenia.14 However, AZD4320, an alternative Bcl-2/xL inhibitor, is being studied in lymphoid malignancies as an intravenous formulation, with hope to mitigate its effect on platelets.15 Therapeutic Antibodies Targeting surface receptors and inducing both direct and immunemediated apoptosis has been a success story in CLL with use of anti-CD20 agents...Lanalumab (VAY-736), a humanized defucosylated engineered antibody directed against BAFF-R, antagonized pro-survival effects of BAFF in CLL cells.16 In a phase 1 study in combination with ibrutinib in 32 patients with CLL, CR was achieved in 38% of patients, and 42% demonstrated undetectable minimal residual disease (uMRD) in the blood/bone marrow, a promising result not expected with ibrutinib alone.17 Alternative targets for therapeutic antibodies include ROR1 (cirmtuzumab) and CD19 (tafasitamab)...A recent report of a phase 1/2 study of lisocabtagene maraleucel, an autologous CD19-directed CAR T-cell therapy (TRANSCEND CLL 004), confi rmed effi cacy in patients with relapsed/refractory CLL.18 In this study, patients had a median of 4 prior therapies, including ibrutinib and venetoclax...In a Phase 1/2 trial, HLA-mismatched CD19-targeting CAR NK cells induced CRs in patients with CLL after a single infusion and without CRS or neurotoxicity attributable to the cellular product.19 Finally, bi-specifi c antibodies have demonstrated impressive effi cacy in non-Hodgkin lymphoma and are also an off-the-shelf product which boasts high tolerability. Development of bi-specifi c antibodies in CLL is still in early stages, however epcoritamab (a subcutaneously administered CD3xCD20 Duobody) demonstrated responses in an ongoing Phase 1 study.20 In sum, targeted therapy replaced chemo-immunotherapy in treatment of CLL, and emerging small molecule and cell therapy approaches auger an expansion of the therapeutic armamentarium for CLL in the next decade.
- |||||||||| Breyanzi (lisocabtagene maraleucel) / BMS, Kymriah (tisagenlecleucel-T) / Novartis, Yescarta (axicabtagene ciloleucel) / Gilead, Daiichi Sankyo
Real-world versus clinical trial CAR T outcomes among patients diagnosed with diffuse large B-cell lymphoma. (Available On Demand; Poster Bd #: F16) - Sep 15, 2022 - Abstract #ASCOQC2022ASCO_QC_485;
Real-world evidence of CAR T is critical for understanding real-world benefit, safety, and value of novel therapies. >1Schuster et al., 2019 (JULIET); 2Neelapu et al., 2017 (ZUMA-1); 3Abramson et al., 2020 (TRANSCEND NHL 001)
- |||||||||| Breyanzi (lisocabtagene maraleucel) / BMS, Yescarta (axicabtagene ciloleucel) / Gilead, Daiichi Sankyo
Journal: Matching-adjusted indirect comparison of axi-cel and liso-cel in relapsed or refractory large B-cell lymphoma. (Pubmed Central) - Sep 2, 2022
Axi-cel was associated with a higher rate of grade ≥3 cytokine release syndrome (odds ratio [OR]: 3.64 [95% CI: 1.04-12.76]) and neurological events (OR: 3.45 [95% CI: 1.65-7.19]), with smaller differences estimated in scenario analyses including ZUMA-1 safety management cohorts. Results suggest axi-cel improved survival compared to liso-cel but with increased odds of specific adverse events.
- |||||||||| Breyanzi (lisocabtagene maraleucel) / BMS, Kymriah (tisagenlecleucel-T) / Novartis, Yescarta (axicabtagene ciloleucel) / Gilead, Daiichi Sankyo
Clinical, Clinical guideline, P3 data, CAR T-Cell Therapy: Role of CD19 CAR T Cells in Second Line Large B Cell Lymphoma: Lessons from Phase 3 Trials - An Expert Panel Opinion from the American Society for Transplantation and Cellular Therapy. (Pubmed Central) - Aug 31, 2022
These three studies, while largely addressing the same question, had different outcomes with ZUMA-7 and TRANSFORM demonstrating a significant improvement with CD19 CAR T-cell therapy in second line compared to SOC, while BELINDA did not show any benefit. The US FDA has now approved axicabtagene ciloleucel for LBCL that is refractory to first-line chemoimmunotherapy or relapses within 12 months of first-line chemoimmunotherapy. Following the reporting of these practice changing studies, a group of experts convened by the American Society for Transplantation and Cellular Therapy now provides a comprehensive review of the three studies, emphasizing potential differences, and share perspectives on what these results mean to clinical practice in this new era of treatment of B-cell lymphomas.
- |||||||||| Breyanzi (lisocabtagene maraleucel) / BMS
Journal: Liso-cel effective in R/R LBCL. (Pubmed Central) - Aug 25, 2022
Lower overall HCRU was observed with outpatient postinfusion monitoring. No abstract available
- |||||||||| Radiotherapy for Relapse after Chimeric Antigen Receptor T Cell Therapy in Hematologic Malignancies (Henry B. Gonzalez Convention Center, Room 214) - Aug 1, 2022 - Abstract #ASTRO2022ASTRO_1448;
Patients received axicabtagene (n=14), lisocabtagene (n=13), tisagenlecleucel (n=9), experimental CAR T (n=4), idecabtagene (n=3), and brexucabtagene (n=1). SRT has promising and diverse utility after CAR T. Prolonged survival can be achieved with SRT bridging to allo/second CAR T or even with definitive SRT in the setting of limited relapse and when it is feasible to irradiate all active disease to a definitive dose.
- |||||||||| Next Questions: Mantle Cell Lymphoma (Level 4, Grand Ballroom G-L) - Jul 26, 2022 - Abstract #SOHO2022SOHO_279;
P2, P3
Chimeric antigen receptor (CAR) T cell therapy is available to patients who progress after second-line therapy and are candidates for this approach with one currently available product (brexucabtagene autoleucel (brexicel))...The OASIS-2 trial is evaluating time-limited “chemo-free” treatment randomizing patients to obinutuzumab + ibrutinib vs obinutuzumab + ibrutinib + the BCL-2 inhibitor venetoclax...The role of BTKi is being evaluated in more intensive combination regimens in both EA4181, a randomized phase II trial evaluating BR + HiDAC vs BR + HiDAC + acalabrutinib vs BR + acalabrutinib (NCT04115631) and TRIANGLE, a randomized phase III trial evaluating alternating R-CHOP/R-DHAP (dexamethasone, cisplatin, cytarabine) followed by ASCT vs the addition of ibrutinib to this regimen followed by ASCT + 2 years of maintenance ibrutinib vs the addition of ibrutinib to this regimen without ASCT but followed by 2 years of maintenance ibrutinib with MR given for up to 3 years in all arms (NCT02858258)...The future role of BTKi in relapse will likely be impacted by its more frequent use in frontline combinations, although data on the non-covalent BTKi pirtobrutinib has shown this agent to have activity in patients who have disease progression on covalent BTKi suggesting a role for BTKi in succession.8 Brexi-cel was the fi rst autologous CD19-directed cellular therapy approved in r/r with an ORR of 93% including 67% CR, a median PFS 25.8 months and OS 47.4 months.9-10 This product has demonstrated similar activity among patients with high-risk disease features including TP53 mutations, blastoid morphology, and high risk MIPI, leading to trials evaluating it in earlier lines of therapy in these patient populations...Lisocabtagene maraleucel is a second autologous CD19-directed cellular therapy that has shown similar effi cacy in a smaller patient population, but with improved toxicity profi le,11 leaving the potential for “safer” products...This provides an “off the shelf ” treatment option with overall lower grade toxicity than reported with CAR products, which may make it more accessible to a larger number of patients and combination will likely emerge. Immunotherapy approaches with antibody drug conjugates (ADC) have shown promise with zilovertamab vedotin13 targeting ROR-1 and loncantuximab tesirine14 targeting CD19 reported to be active in r/r MCL, with plans for further evaluation.
- |||||||||| Immunotherapeutic Options for Patients with MCL Who Progress on BTK Inhibitors (Level 4, Grand Ballroom G-L) - Jul 26, 2022 - Abstract #SOHO2022SOHO_232;
The overall response rate was 81%, and 67% of patients achieved a complete response.11 Epcoritamab, which can be administered subcutaneously, is also active in this setting, and other bispecifi c antibodies continue to be investigated.12 It remains to be seen whether this class will supplant CAR-T or be used as an additional therapy option for patients before or after CAR-T treatment...Future studies will explore the role of immunotherapy earlier in the treatment course, especially for highrisk patients, and proper sequencing of BTK inhibitors, cellular therapies, novel antibodies, and bispecifi c antibodies will need to be determined through additional investigation. Evaluation of combination therapies which incorporate BTK inhibitors and other targeted agents with immunotherapies may induce deeper, longlasting remissions, which further improve OS for all patients.
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