In diffuse large B-cell lymphoma (DLBCL), the most common non-Hodgkin lymphoma (NHL), 50-60% of patients are cured with R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone) chemoimmunotherapy in the first line.¹ Meanwhile, patients with early-stage Hodgkin lymphoma (HL) are typically treated with ABVD (doxorubicin, bleomycin, vinblastine, dacarbazine) chemotherapy followed by radiation.²

One of the most critical developments in the treatment of these diseases over the last few years is the addition of novel agents to existing chemotherapy backbones. Just last year for example, the ECHELON-1 (NCT01712490) Phase III study found combining antibody-drug conjugate (ADC) brentuximab vedotin with AVD (doxorubicin, vinblastine, dacarbazine) chemotherapy prolonged overall survival (OS), progression-free survival (PFS), and reduced the need for subsequent therapy in patients with advanced-stage HL.³ This led to the regimen becoming a preferred frontline option for these patients.²  

In this video, Swetha Kambhampati, MD, City of Hope, Duarte, CA, highlights how novel agents are being combined with chemotherapy in both the frontline and salvage treatment of HL. She discusses the ECHELON-1 study, and expresses her excitement over an ongoing Phase III trial (NCT03907488) comparing the outcomes of patients with newly diagnosed stage III or IV classic HL treated with either nivolumab or brentuximab vedotin in combination with chemotherapy. 

Hodgkin lymphoma 

In addition to the implementation of novel agents, risk- and response-adapted treatment strategies are emerging in the lymphoma field. In HL, for instance, choice of treatment is dependent on factors such as disease histology and stage,² the presence of poor prognostic features and bulky disease (a single site of disease >10 cm in diameter),² as well as patient age, sex and comorbidities.⁶ Moreover, positron emission tomography (PET) scanning is being implemented in the course of treatment for HL to guide treatment de-escalation and intensification decisions.^2,7 

Diffuse large B-cell lymphoma 

In DLBCL, a key aspect of treatment selection is whether patients are double or triple hit,⁹ as high-grade B-cell lymphomas with MYC and BCL2 or BCL6 rearrangements have been shown to have poor outcomes with upfront R-CHOP.^10-12 Although no optimal treatment has been established for these patients,¹³ dose-adjusted (DA) EPOCH-R (etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, and rituximab)¹⁴ and high intensity regimens such as R-Hyper-CVAD (rituximab, cyclophosphamide, vincristine, doxorubicin, and dexamethasone alternating with high-dose methotrexate and cytarabine) are recommended by the NCCN 2023 guidelines over R-CHOP.¹³

Here, Gerardo Musuraca, MD, of the IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST), Meldola, Italy, discusses the current approach to managing DLBCL, highlighting the importance of identifying double and triple hit molecular subtypes. 

PET-guided risk-adaptation strategies are also under investigation in DLBCL.⁵ A recent study found PET scanning after two cycles of chemotherapy (PET2) could predict which patients were at high risk of progression and death in two large independent prospective cohorts.¹⁵ The authors advise that, since they could benefit patients, such PET-guided risk-adapted therapy strategies should be the focus of clinical trials.¹⁵ 

Here, Krish Patel, MD, of the Swedish Cancer Institute, Seattle, WA, comments on the results of a Phase II trial (NCT03736616) assessing a novel salvage regimen of acalabrutinib plus R-ICE (rituximab, ifosfamide, carboplatin, etoposide) chemotherapy in transplant–eligible patients with R/R DLBCL.¹⁶ The study met its endpoint of improving the complete response (CR) rate in these patients and, as Dr Patel explains, after three cycles of therapy, 50% of patients in the current cohort achieved CR, compared with 30% in the historical control. Additionally, almost 70% of patients were able to be taken to potentially curative ASCT.