2022 American Society of Hematology (ASH) Annual Meeting

Jeremiah Moore, PharmD, BCOP

Moore ASH 2022 (002)

Hematology/Oncology Clinical Pharmacy Specialist

UR Specialty Pharmacy

James P. Wilmot Cancer Institute

University of Rochester Medical Center

Rochester, NY

Introduction

The 64th American Society of Hematology (ASH) annual meeting took place December 10-13, 2022 in New Orleans, Louisiana as well as virtually. The ASH annual meeting is the largest gathering of hematology experts in the world with the latest advances and emerging data in malignant and benign hematology shared through educational sessions, oral abstracts, and research posters.

The following is a summary of select abstracts with the potential to be practice changing including the phase 3 E1910 trial showing an overall survival benefit with the addition of blinatumomab in newly diagnosed B-ALL MRD negative patients; the ALPINE trial showing improved progression-free survival with zanubrutinib versus ibrutinib in relapsed CLL/SLL; the APPLY-PNH study of iptacopan an oral complement inhibitor; the MATRix trial investing the role of autologous stem cell transplant in primary CNS lymphoma, and the BMT CTN 1703 trial comparing GVHD prophylaxis regimens cyclophosphamide/tacrolimus/mycophenolate mofetil (PTCy/Tac/MMF) or tacrolimus/methotrexate (Tac/MTX).

Results from the ECOG-ACRIN E1910 randomized phase III trial1

Mark Litzow, MD presented the results of ECOG-ACRIN E1910 trial in which adult patients with newly diagnosed BCR-ABL1 negative B-ALL achieving a complete remission following induction chemotherapy and minimal residual disease (MRD) negativity (≤ 0.01%) after intensification chemotherapy were randomized to standard of care consolidation chemotherapy with or without the bi-specific CD19-directed CD3 T-cell engager blinatumomab. Two hundred twenty-four patients with a median age of 51 years (range 30-70) were randomized, 112 to each arm. The primary endpoint of overall survival (OS), at a median follow up of 43 months, significantly favored the blinatumomab arm (median OS: not reached vs. 71.4 months, HR 0.42, 95% CI: 0.24 – 0.75; p=0.003). Twenty-two patients in each arm proceeded to allogeneic stem cell transplant. The authors concluded the addition of blinatumomab to consolidation chemotherapy in newly diagnosed BCR-ABL1 negative B-ALL patients who were MRD negative after intensification chemotherapy significantly improved OS with no significant safety concerns.

Results from the ALPINE study of zanubrutinib versus ibrutinib in relapsed/refractory (R/R) chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL)2

Jennifer Brown, MD, PhD presented the results of the randomized phase 3 ALPINE study in which 652 patients with R/R CLL/SLL patients were randomized to either ibrutinib (n= 325) or zanubrutinib (n=327) until disease progression or unacceptable toxicity. The median prior lines of therapy was one. At a median follow-up of 29.6 months, the primary endpoint of overall response rate (ORR), as assessed by independent review committee, favored zanubrutinib versus ibrutinib arm (86.2 vs 75.7%, p=0.0007). Progression-free survival (PFS) in the intent-to-treat (ITT) population was greater in the zanubrutinib versus ibrutinib arm (median PFS: not reached vs. 35 months, HR 0.65; p=0.0024). The side effect profile favored zanubrutinib with lower rates of treatment discontinuation, interruptions, and dose reductions as compared to ibrutinib. The authors concluded that zanubrutinib is more efficacious and better tolerated than ibrutinib as treatment for R/R CLL/SLL.

Results from the phase III APPLY-PNH study of iptacopan versus eculizumab or ravulizumab3

Regis Peffault de Latour, MD, PhD presented the results of the APPLY-PNH study in which 97 adult paroxysmal nocturnal hemoglobinuria (PNH) patients with persistent anemia (defined as mean hemoglobin [Hb] <10 g/dL) on complement C5 inhibitor therapy with eculizumab or ravulizumab for ≥ 6 months were randomized to the oral, factor B complement inhibitor, iptacopan 200 mg twice daily (n=62) or continued complement C5 inhibitor therapy (n=35) for 24 weeks. There were two primary endpoints, the percentage of patients with an increase from baseline in Hb ≥ 2 g/dL and Hb ≥ 12 g/dL in the absence of red blood cell transfusion.

Iptacopan resulted in 85% of patients achieving a Hb ≥ 2g/dL versus 0% in the complement 5 inhibitor arm and 70% of iptacopan patients achieved a Hb ≥ 12 g/dL versus 0% in the complement 5 inhibitor arm (p<0.0001). Headache and diarrhea were more common in the iptacopan arm with infections and break through hemolysis more common in the complement C5 inhibitor arm. The authors concluded that iptacopan therapy in this trial was superior to complement C5 inhibitor therapy and has the potential to be a new standard of care in PNH.

Results of the phase III MATRix/IELSG43 trial in primary central nervous lymphoma (PCNSL)4

Gerald Illerhaus, MD presented the results of the randomized trial, in which 346 patients with newly diagnosed PCNSL received induction therapy with MATRix (rituximab, methotrexate, cytarabine, thiotepa), followed by randomization to non-myeloablative R-DeVIC (rituximab, dexamethasone, etoposide, ifosfamide, carboplatin) (n=115) or high-dose consolidation chemotherapy (carmustine and thiotepa) followed by autologous stem cell transplant (HD-ASCT) (n =114). At a median follow up of 44 months the primary endpoint of PFS at 3 years favored the HD-ASCT arm at 79% (95% CI 71-86) vs R-DeVIC arm at 53% (95% CI 43-62) (HR 0.42, p=0.0003). Based on the significantly better outcomes with HD-ASCT with no significant differences in neurocognitive functions, the authors concluded that HD-ASCT is the standard consolidation therapy for suitable PCNSL patients.

Results from phase III blood and marrow transplant clinical trials network (BMT CTN) 1703 trial5

Shernan Holtan, MD presented the results of the BMT CTN 1703 trial in which 431 adult patients were randomized to either cyclophosphamide/tacrolimus/mycophenolate mofetil (PTCy/Tac/MMF) (n=214) or tacrolimus/methotrexate (Tac/MTX) (n=217) following a reduced intensity allogeneic hematopoietic stem cell transplant with 6/6 matched related (n=128), 8/8 matched unrelated (n=288) or 7/8 (n=15) peripheral blood stem cell donor. The primary endpoint was 1-year Graft-Versus-Host-Disease (GVHD) free, relapse free survival (GRFS), which was defined as grade III-IV acute GVHD, chronic GVHD requiring systemic immune suppression, relapse or progression, or death. The primary disease for which transplant was indicated was acute myeloid leukemia and myelodysplastic syndrome. GRFS at 1 year significantly favored the PTCy/Tac/MMF arm at 52.7% vs Tac/MTX arm at 34.9%, (HR 0.641, 95% CI 0.492 – 0.835, p=0.001). The authors concluded that PTCy/Tac/MMF significantly improved 1-year GRFS without increased risk of relapse or death and should become the standard GVHD prophylaxis regimen for closely matched donors.

Conclusion

There was a wealth of research shared across multiple hematology disciplines at this year’s ASH annual meeting. In addition to the late-breaking abstracts shared above, exciting research was presented on novel therapies such as the Bruton’s tyrosine kinase-targeted protein degrader6, bispecific antibodies7-9, Chimeric Antigen Receptor T-cell (CAR-T) therapies10,11, and a pharmacist driven iron deficiency management clinic12. I would encourage you to investigate the more than 3,000 abstracts available at www.hematology.org/meetings/annual-meeting/abstracts.

Recommended Reading/References:

  1. Litzow MR, Sun Z, Paietta E, et al. Consolidation Therapy with Blinatumomab Improves Overall Survival in Newly Diagnosed Adult Patients with B-Lineage Acute Lymphoblastic Leukemia in Measurable Residual Disease Negative Remission: Results from the ECOG-ACRIN E1910 Randomized Phase III National Cooperative Clinical Trials Network Trial. Blood. 2022;140(Supplement 2):LBA-1-LBA-1.
  2. Brown JR, Eichhorst B, Hillmen P, et al. Zanubrutinib Demonstrates Superior Progression-Free Survival (PFS) Compared with Ibrutinib for Treatment of Relapsed/Refractory Chronic Lymphocytic Leukemia and Small Lymphocytic Lymphoma (R/R CLL/SLL): Results from Final Analysis of ALPINE Randomized Phase 3 Study. Blood. 2022;140(Supplement 2):LBA-6-LBA-6.
  3. Peffault de Latour R, Roeth A, Kulasekararaj A, et al. Oral Monotherapy with Iptacopan, a Proximal Complement Inhibitor of Factor B, Has Superior Efficacy to Intravenous Terminal Complement Inhibition with Standard of Care Eculizumab or Ravulizumab and Favorable Safety in Patients with Paroxysmal Nocturnal Hemoglobinuria and Residual Anemia: Results from the Randomized, Active-Comparator-Controlled, Open-Label, Multicenter, Phase III Apply-PNH Study. Blood. 2022;140(Supplement 2):LBA-2-LBA-2.
  4. Illerhaus G, Ferreri AJM, Binder M, et al. Effects on Survival of Non-Myeloablative Chemoimmunotherapy Compared to High-Dose Chemotherapy Followed By Autologous Stem Cell Transplantation (HDC-ASCT) As Consolidation Therapy in Patients with Primary CNS Lymphoma - Results of an International Randomized Phase III Trial (MATRix/IELSG43). Blood. 2022;140(Supplement 2):LBA-3-LBA-3.
  5. Holtan SG, Hamadani M, WU J, et al. Post-Transplant Cyclophosphamide, Tacrolimus, and Mycophenolate Mofetil As the New Standard for Graft-Versus-Host Disease (GVHD) Prophylaxis in Reduced Intensity Conditioning: Results from Phase III BMT CTN 1703. Blood. 2022;140(Supplement 2):LBA-4-LBA-4.
  6. Mato AR, Wierda WG, Ai WZ, et al. NX-2127-001, a First-in-Human Trial of NX-2127, a Bruton's Tyrosine Kinase-Targeted Protein Degrader, in Patients with Relapsed or Refractory Chronic Lymphocytic Leukemia and B-Cell Malignancies. Blood. 2022;140(Supplement 1):2329-2332.
  7. Bumma N, Richter J, Brayer J, et al. Updated Safety and Efficacy of REGN5458, a BCMAxCD3 Bispecific Antibody, Treatment for Relapsed/Refractory Multiple Myeloma: A Phase 1/2 First-in-Human Study. Blood. 2022;140(Supplement 1):10140-10141.
  8. Kim TM, Taszner M, Cho S-G, et al. Odronextamab in Patients with Relapsed/Refractory (R/R) Follicular Lymphoma (FL) Grade 1-3a: Results from a Prespecified Analysis of the Pivotal Phase II Study ELM-2. Blood. 2022;140(Supplement 1):2280-2282.
  9. Matasar MJ, Cheah CY, Yoon DH, et al. Subcutaneous Mosunetuzumab in Relapsed or Refractory B-Cell Lymphoma: Promising Safety and Encouraging Efficacy in Dose Escalation Cohorts. Blood. 2020;136(Supplement 1):45-46.
  10. Bansal R, Paludo J, Hathcock MA, et al. Outpatient Practice Pattern for Recently Approved CAR-T in Patients with Lymphoma and Multiple Myeloma. Blood. 2022;140(Supplement 1):2399-2401.
  11. Park JH, Palomba ML, Rivière I, et al. A Phase I Study of CD19-Targeted 19(T2)28z1xx CAR T Cells in Adult Patients with Relapsed or Refractory Diffuse Large B-Cell Lymphoma. Blood. 2022;140(Supplement 1):403-404.
  12. Freydman J, AlDoughaim M, Gorelikov S, et al. Fe-Armacist Run Iron Deficiency Management Clinic to Optimize Intravenous Iron Infusions in an Ambulatory Oncology Clinic. Blood. 2022;140(Supplement 1):5003-5004.