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

Kieron Dunleavy, MD, a staff clinician with the National Cancer Institute in Bethesda, MD, explains that the molecular subtype of diffuse large B cell lymphoma (DLBCL), known as primary mediastinal B cell lymphoma (PMBL), has a molecular profile that is more similar to Hodgkin lymphoma than other subtypes of DLBCL, which makes it difficult to treat.

Overall, the standard treatment for DLBCL is R-CHOP (rituximab—cyclophosphamide, doxorubicin, vincristine, and prednisone), however, this regimen has not been effective at treating patients with PMBL. This subtype remains an area that requires novel approaches and dose intensity modifications.

Dunleavy explains that one approach being researched involves adjusting the dose intensity of the regimen EPOCH (etoposide, prednisone, vincristine [Oncovin] and doxorubicin hydrochloride [hydroxydaunorubicin hycrochloride]) in combination with rituximab (EPOCH-R). This approach was tested in 46 patients and resulted in mediastinal radiation being obviated in approximately 95% of the cases, making it an ideal treatment for PMBL.

Dr. Kieron Dunleavy, from the National Cancer Institute, Discusses Treatment Options for Primary Mediastinal B Cell Lymphoma

Dr. Dunleavy Discusses Treatment Options for PMBL

Kieron Dunleavy, MD, a staff clinician with the National Cancer Institute in Bethesda, MD, discusses research into novel treatments for activated B-cell (ABC) diffuse large B-cell lymphoma (DLBCL).

The standard of care for ABC DLBCL is generally associated with significantly worse outcomes than observed in germinal center B-cell DLBCL. Current research is focused on finding novel agents that target the pathways implicated in the ABC subtype in order to improve the prognosis.

Researchers recently found that chronic active B-cell receptor (BCR) signaling is an important factor in ABC DLBCL. Bruton’s tyrosine kinase (Btk) is a central mediator of BCR signaling. Inhibiting this target prevents malignant B-cells from migrating and induces apoptosis.

The first agent to inhibit Btk, known as PCI-32765, is currently under investigation in order to determine its efficacy.

Dr. Kieron Dunleavy, from the National Cancer Institute, Discusses ABC DLBCL Research

Dr. Dunleavy Discusses ABC DLBCL Research

Kieron Dunleavy, MD, a staff clinician with the National Cancer Institute in Bethesda, MD, discusses the changes that have occurred in the understanding of diffuse large B-cell lymphoma (DLBCL) in the past 10-15 years.

DLBCL is the most common subtype of non-Hodgkin's lymphoma. Louis Staudt, MD, PhD, and the Lymphoma/Leukemia Molecular Profiling Project (LLMPP), which focused on the identification of distinct subtypes of DLBCL using gene expression profiling, largely defined the understanding of its taxonomy.

Research from the LLMPP resulted in 3 distinct molecular subtypes of DLBCL. Each type expressed unique characteristics, the first demonstrated germinal center B-cells, the second type showed gene activations in the peripheral blood B-cells, and the primary mediastinal B-cell type.

The delineation of 3 DLBCL subtypes provides the potential to find novel agents and treatment that affects each type specifically. Targeted approaches and agents are currently being investigated.

Dr. Kieron Dunleavy from the National Cancer Institute Discusses 3 Molecular Subtypes of DLBCL 

Kieron Dunleavy, MD

Articles

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

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

Dr. Dunleavy Discusses Treatment Options for PMBL

Dr. Dunleavy Discusses ABC DLBCL Research

Dr. Dunleavy Discusses 3 Molecular Subtypes of DLBCL