Data from the following clinical trials are discussed:

ASCO 7521: ASPEN: Long-term follow-up results of a phase 3 randomized trial of zanubrutinib (ZANU) versus ibrutinib (IBR) in patients with Waldenström macroglobulinemia (WM)

EHA P1120: The Efficacy and Safety of Zanubrutinib and Dexamethasone in Symptomatic Waldenstrom Macroglobulinemia

EHA P1160: Results of a Phase 2 Expanded Access Study of Zanubrutinib in Patients with Waldenstrom Macroglobulinemia

ASCO 7510: Zanubrutinib plus obinutuzumab (ZO) versus obinutuzumab (O) monotherapy in patients (pts) with relapsed or refractory (R/R) follicular lymphoma (FL): Primary analysis of the phase 2 randomized ROSEWOOD trial

ASCO 7511: Efficacy and safety of zandelisib administered by intermittent dosing (ID) in patients with relapsed or refractory (R/R) follicular lymphoma (FL): Primary analysis of the global phase 2 study TIDAL

ASCO 7524: Subcutaneous epcoritamab with rituximab + lenalidomide (R2) in patients (pts) with relapsed or refractory (R/R) follicular lymphoma (FL): Update from phase 1/2 trial

Videos

Shared insight from expert oncologists on key clinical trial data in lymphomas from the ASCO 2022 and EHA 2022 Annual Meetings.

Lymphomas Trial Data From the ASCO 2022 and EHA 2022 Annual Meetings 

ASCO 7009: A phase II trial of a chemotherapy-free combination of ponatinib and blinatumomab in adults with Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL)

ASCO e19003: A phase 1b study of blinatumomab with the anti-programmed cell death (PD)-1 antibody AMG 404 in adults with relapsed/refractory (R/R) B-cell precursor acute lymphoblastic leukemia (ALL)

ASCO 7034: A phase II study of hyper-CVAD with sequential blinatumomab (Blina), with or without inotuzumab ozogamicin (INO), in adults with newly diagnosed B-cell acute lymphoblastic leukemia (ALL)

ASCO 7011: Updated results from a phase II study of mini-hyper-CVD (mini-HCVD) plus inotuzumab ozogamicin (INO), with or without blinatumomab (Blina), in older adults with newly diagnosed Philadelphia chromosome (Ph)-negative B-cell acute lymphoblastic leukemia (ALL)

EHA P353: Forty Months of the Gimema LAL2116 (D-ALBA) Protocol and Ancillary LAL2217 Study for Newly Diagnosed Adult PH+ ALL

EHA P366: Blinatumomab Added to Prephase and Consolidation Therapy in Newly Diagnosed Precursor B-ALL in Adults. A Phase II Hovon Trial

EHA PB1762: Ponatinib Versus Imatinib with Reduced – Intensity Chemotherapy in Patients with Newly Diagnosed Philadelphia Chromosone-Positive (PH+) Acute Lymphoblastic Leukemia (ALL): PHALLCON Study

EHA PB1749: Apoptotic Effect of Flumatinib Combined with BCL2 Inhibitor on PH+ B-Cell Acute Lymphoblastic Leukemia

Expert oncologist perspectives on key clinical trial data in acute lymphocytic leukemia from the ASCO 2022 and EHA 2022 Annual Meetings.

Acute Lymphocytic Leukemia Trial Data From the ASCO 2022 and EHA 2022 Annual Meetings

Jae H. Park, MD, hematologic oncologist, Memorial Sloan Kettering Cancer Center, discusses emerging CAR T-cell therapies in hematologic malignancies. 

Allogeneic CAR T-cell therapies are emerging for use in hematologic malignancies, such as leukemia, lymphoma, and multiple myeloma, as a potential strategy to shorten manufacturing time and increase accessibility to immune effector cell therapy, Park says. Further data are needed to determine if the off-the-shelf approach will yield similar rates of durable remission compared with autologous CAR T-cell therapies, Park adds. Additionally, some allogeneic products are utilizing modified or unmodified natural killer cells rather than T cells, Park explains.

Another emerging strategy is with dual-targeting CAR T-cell therapy, Park says. Particularly in leukemia, antigen escape has been observed as a driver of treatment resistance, Park explains. Dual-targeting therapies have the potential to overcome antigen escape, Park adds.

In acute myeloid leukemia (AML), cellular therapy has not demonstrated significant success because myeloid and leukemic cells do not express an exclusive target, Park says. As such, dual-targeted or armored CAR T-cell therapies could overcome tumor microenvironment resistance and effectively treat AML, other hematologic malignancies, and some solid tumors, Park concludes.

Jae H. Park, MD, discusses emerging CAR T-cell therapies in hematologic malignancies.  



Dr. Park on Emerging CAR T-Cell Therapies in Hematologic Malignancies 

Jae H. Park, MD, attending physician, Leukemia Service and Cellular Therapeutics Center, Memorial Sloan Kettering Cancer Center, discusses potential alternate CAR T-cell targets in B-cell malignancies.

Though significant response rates have been demonstrated with CD19-targeting CAR T-cells, investigation into other possible B-cell antigen targets are ongoing, says Park. CD22 is of particular interest, though responses do not appear as durable as those seen with CD19-targeting antigens.

Additionally, dual-targeting CAR T-cell therapy may increase response rates in this field. At the 2019 ASH Annual Meeting, an update from a phase I dose-climbing study (ChiCTR1800018143) showed objective response rates of over 90% was shown with CAR T-cells targeting both CD38 and BCMA in patients with extramedullary multiple myeloma.

Jae H.Park, MD, discusses potential alternate CAR T-cell targets in B-cell malignancies.

Dr. Park on Potential Alternate CAR T-Cell Targets in B-Cell Malignancies

Jae H. Park, MD, attending physician, Leukemia Service and Cellular Therapeutics Center, Memorial Sloan Kettering Cancer Center, discusses encouraging data with CAR T-cell therapy in acute lymphoblastic leukemia (ALL). 

Initial data with CAR T-cell therapy showed a complete response rate of approximately 80% in pediatric and adult patients with relapsed/refractory ALL, says Park. Although approximately 40% of patients will relapse early, some patients can experience durable responses lasting 3 to 5 years. 

Ongoing research is evaluating which patients will benefit the most from this strategy, explains Park. The goal is to minimize toxicity and improve remission durations while retaining efficacy. To date, patients with lower disease burden appear to derive the greatest benefit from CAR T-cell therapy. 

Ongoing trials are exploring additional targets with the goal of minimizing, and ultimately eliminating, toxicity, concludes Park. 

Jae H. Park, MD, discusses encouraging data with CAR T-cell therapy in acute lymphoblastic leukemia. 
 

Dr. Park on Updates With CAR T Cells in ALL

Jae H. Park, MD, attending physician, Leukemia Service and Cellular Therapeutics Center, Memorial Sloan Kettering Cancer Center, discusses the use of chimeric antigen receptor (CAR) T-cell therapy in the treatment of patients with acute lymphoblastic leukemia (ALL).

CAR T cells have proven to be an effective treatment option, and there is an FDA approval for the CD19-targeted therapy tisagenlecleucel (Kymriah) for use in pediatric and young adult patients with relapsed/refractory disease. This product has shown efficacy even in patients who have progressed on 3 or 4 lines of prior therapy.

However, there are several challenges that need to be addressed with CAR T-cell therapy moving forward, Park says. Mainly, oncologists still do not know how to minimize the risk of relapse in these patients. Ongoing research is looking to tackle this issue by further modifying CAR T cells or combining this therapy with other modalities. Eventually, Park notes, CAR T cells could be moved into the earlier treatment settings as opposed to being used in the third or fourth line. In addition, it would be useful to have an FDA-approved CAR T-cell product for the treatment of adult patients with ALL, as tisagenlecleucel is only approved for patients up to age 25.

Jae H. Park, MD, attending physician, Leukemia Service and Cellular Therapeutics Center, Memorial Sloan Kettering Cancer Center, discusses the use of CAR T cells in the treatment of patients with acute lymphoblastic leukemia.

Dr. Park Discusses Use of CAR T Cells in ALL

Jae H. Park, MD, attending physician, Leukemia Service and Cellular Therapeutics Center, Memorial Sloan Kettering Cancer Center, discusses a particular challenge he sees in using chimeric antigen receptor (CAR) T-cell therapies in patients with acute myeloid leukemia (AML).

For now, the data is still too early, but it has been encouraging, Park says, when looking at CD33 and CD123 in patients with AML. However, these targets are not as good as CD19. Park says further investigation is necessary to identify better targets in this space.

Jae H. Park, MD, discusses a particular challenge he sees in using CAR T-cell therapies in patients with acute myeloid leukemia.

Jae H. Park, MD

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