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Epcoritamab in R/R LBCL

 

Non-Hodgkin lymphoma (NHL) is a heterogeneous disease with over 80 subtypes, and is reported to be the most common hematological malignancy worldwide.1,2 The treatment landscape of NHL has transformed rapidly in recent years with the development of novel immunotherapies, including antibodies and chimeric antigen receptor T-cell (CAR-T) therapy.2 While these immunotherapies have greatly improved outcomes for patients, the treatment and management of relapsed/refractory (R/R) disease remains a challenge.3 Several immunotherapies are also being explored for the treatment of relapsed disease, with bispecific antibodies continuing to show promise.

Epcoritamab is a novel CD3-CD20 bispecific antibody being investigated for the treatment of R/R NHL. CD20 is a cell surface antigen expressed on mature B-cells, and therefore represents an attractive target for the treatment of B-cell malignancies, including non-Hodgkin lymphoma.4 The safety and efficacy of epcoritamab for the treatment of R/R NHL is being evaluated in several ongoing clinical trials, and preliminary results from one of these studies were reported at the 2022 European Hematology Association (EHA) meeting.

In this video, Catherine Thieblemont, MD, PhD, Saint-Louis University Hospital, Paris, France, shares some results from a Phase II study evaluating subcutaneous epcoritamab in patients with R/R large B-cell lymphoma (LBCL) (NCT03625037).

 

The study reported an overall response rate (ORR) of 63% and a complete response rate of 39%, which is encouraging for such a heavily pre-treated population. Patients receiving epcoritamab reported some mild toxicities, including mainly grade 1 and grade 2 cytokine release syndrome (CRS). Very few cases of immune effector cell-associated neurotoxicity syndrome (ICANS) were reported in the study.

ECHELON-1 trial updates: overall survival data

 

Brentuximab vedotin is a CD30-targeting antibody-drug conjugate (ADC) that was approved by the US Food and Drug Administration for the treatment of classical Hodgkin lymphoma (HL) in 2018, and has greatly transformed the HL treatment landscape.5,6

 

The approval of this agent in the frontline setting was based on the promising results obtained in the Phase III ECHELON-1 trial (NCT01712490), comparing the use of brentuximab vedotin plus doxorubicin, vinblastine, and dacarbazine (A+AVD) versus doxorubicin, bleomycin, vinblastine and dacarbazine (ABVD) for the treatment of classical HL. This trial recently reported an overall survival (OS) advantage of 93.9% with A+AVD vs 89.4% with ABVD. These findings may further impact treatment approaches in Hodgkin lymphoma.

In this video, Graham Collins, MA, MBBS, MRCP, FRCPath, DPhil, Oxford University Hospitals NHS Foundation Trust, Oxford, UK, shares some insights into the recently reported OS data presented at the 2022 European Hematology Association (EHA) and American Society of Clinical Oncology (ASCO) meetings. Dr Collins first comments on the impact of this the OS survival advantage, and then goes on to discuss the potential benefit of using A+AVD in high-risk patients, as well as how these findings may impact HL treatment in the UK.

Dr Collins concludes “even though I’m quite a fan of using more intensive approaches in younger, high-risk patients like escalated BEACOPDac, there is a cohort of patients who are 45, 50, 55, 60, who I wouldn’t give that to, and if they have high-risk disease, I’d much rather use A2VD now than an ABVD-based approach based on that data.”

Updated PFS results of the GAIA/CLL13 trial

 

The treatment of unfit and elderly patients with chronic lymphocytic leukemia (CLL) has been transformed with the use of targeted therapy including Bruton’s tyrosine kinase (BTK) inhibitors, and the approval of venetoclax-based chemotherapy-free regimens. However, chemoimmunotherapy remains the standard of care for fit patients with CLL, with fludarabinecyclophosphamiderituximab (FCR) commonly given to younger patients, and bendamustine–rituximab (BR) given to older patients.7 Many experts agree that changes should be made to standard of care treatment approaches for fit patients with CLL.

The GAIA/CLL13 trial (NCT02950051) compared the safety and efficacy of time-limited venetoclax-based regimens to standard of care chemoimmunotherapy in fit patients with previously untreated CLL. In this video, Barbara Eichhorst, MD, University of Cologne, Cologne, Germany, shares some updated results from the GAIA/CLL13 trial. In this trial, patients were randomized to either receive chemoimmunotherapy or one of three venetoclax-based regimens: venetoclax plus rituximab (RV), venetoclax plus obinutuzumab (GV), or venetoclax plus obinutuzumab and ibrutinib (GIV).

There are two co-primary endpoints being evaluated: measurable residual disease (MRD), which was presented at the 2021 American Society of Hematology (ASH) meeting, and progression-free survival (PFS), which was presented at the 2022 European Hematology Association meeting.

 

Results from this trial indicate that time-limited therapy with GIV and GV are superior to chemoimmunotherapy with respects to PFS and undetectable MRD. Regarding adverse events, the rate of severe infections was reported to be higher in the GIV arm, and there were higher rates of secondary neoplasia observed in the chemoimmunotherapy arm.

Ponatinib and blinatumomab for the treatment of Ph+ ALL

 

Acute lymphoblastic leukemia (ALL) is an aggressive heterogeneous disease associated with a high mortality rate. However, several advances have been made in recent years to better understand the biology of this disease and improve treatment options for patients.8 Antibody-based therapies continue to attract attention in this field, with several clinical trials reporting promising outcomes.9

 

The Philadelphia (Ph) chromosome is the most common cytogenetic aberration found in adult patients with ALL, and novel chemotherapy-free regimens are transforming the treatment landscape of patients with Ph+ disease.10,11

Blinatumomab, an FDA-approved CD3-CD19 bispecific antibody, has transformed the treatment of relapsed/refractory (R/R) ALL and continues to show promise, and several combinations with this antibody are being evaluated for the treatment of Ph+ ALL. In this video, Nicholas Short, MD, University of Texas MD Anderson Cancer Center, Houston, TX, shares some updated results from an ongoing Phase II study evaluating the safety and efficacy of ponatinib plus blinatumomab in Ph+ ALL. Treatment with this combination has demonstrated high rates of measurable residual disease (MRD) negative responses, as well as response rates in patients with R/R disease. The toxicity profile of this combination was also reported to be manageable with dose mitigation strategies.

 

References

    1. Thandra KC, Barsouk A, Saginala K, et al. Epidemiology of Non-Hodgkin’s Lymphoma. Medical Sciences (Basel). 2021 January 30;9(1):5.
    2. Bezombes C, Pérez-Galán P. Immunotherapies in Non-Hodgkin’s Lymphoma. Cancers (Basel). 2021 July 20;13(14):3625.
    3. Banerjee T, Vallurupalli A. Emerging new cell therapies/immune therapies in B-cell non-Hodgkin’s lymphoma. Current Problems in Cancer. 2022 February;46(1):100825.
    4. van der Horst HJ, de Jonge AV, Hiemstra IH, et al. Epcoritamab induces potent anti-tumor activity against malignant B-cells from patients with DLBCL, FL and MCL, irrespective of prior CD20 monoclonal antibody treatment. Blood Cancer Journal. 2021 February 18;11(2):38.
    5. Lai C, Kandahari AM, Ujjani C. The Evolving Role of Brentuximab Vedotin in Classical Hodgkin Lymphoma. Blood and Lymphatic Cancer. 2019 December 9;9:63-71.
    6. US Food and Drug Administration. Brentuximab Vedotin. Available from https://www.fda.gov/drugs/resources-information-approved-drugs/brentuximab-vedotin?elq=47ad49633b2c4274a2e8458454ae8ff7&elqCampaignId=2089&elqTrackId=14fb2a21e04e454981fa4e97e0f3c62e&elqaid=2844&elqat=1&utm_campaign=Oncology%203/20&utm_medium=email&utm_source=Eloqua (Last accessed 06/07/2022)
    7. Fresa A, Autore F, Galli E, et al. Treatment Options for Elderly/Unfit Patients with Chronic Lymphocytic Leukemia in the Era of Targeted Drugs: A Comprehensive Review. Journal of Clinical Medicine. 2021 October 30;10(21):5104.
    8. Yilmaz M, Kantarjian H, Jabbour E. Treatment of acute lymphoblastic leukemia in older adults: now and the future. Clinical Advances in Hematology & Oncology. 2017 April;15(4):266-274.
    9. Li L, Wang Y. Recent updates for antibody therapy for acute lymphoblastic leukemia. Experimental Hematology & Oncology. 2020 November 27;9(1):33.
    10. Liu-Dumlao T, Kantarjian H, Thomas DA, et al. Philadelphia-positive acute lymphoblastic leukemia: current treatment options. Current Oncology Reports. 2012 October;14(5):387-94.
    11. Ofran Y. A chemotherapy-free regimen for Philadelphia chromosome-positive acute lymphoblastic leukemia: are we there yet? Haematologica. 2021 July 1;106(7):1781-1782.
Written by Anya Dragojlovic-Kerkache