
This report has been written by Yasmina Serroukh and represents an impression of the meeting with some take home messages subjectively selected. It is not meant as a scientific summary.
Aggressive lymphomas
The meeting started with a case-based discussion of DLBCL by Anna Ossami-Saidy. It was a complex but very pedagogic case starting from diagnosis, staging and prognosis assessment. We then could discuss the first line therapy choice and then all the way to 4th line including CAR-T, bispecifics and allogeneic stem cell transplantation.
Following the case, Bertram Glass presented the treatment algorithm of DLBCL in 2024, highlighting the progress that has been made in the last few years. He reminded us that the decision to avoid anthracyclines in first line because of cardial frailty has consequences with an expected inferior OS. The second line landscape is now dominated by CAR-T cell therapy according to the ZUMA-7 and TRANSFORM trials. In transplant ineligible patients PolaBR had been standard of care. However as the use of Polatuzumab is moving to front line its position in relapsed-refractory setting will be questioned. An alternative could be Tafasitamab-lenalidomide based on the L-MIND study but real world data are disappointing in patients with progressive high burden disease. Next option discussed is loncastuximab a CD19 antibody drug conjugated but as it targets the same antigen as available CAR-T cell therapy its position in the algorithm is not defined. Finally, the second revolution in the field, after CAR-T cell therapy is the development of bispecific antibodies: the data on epcoritamab and glofitamab were discussed. A quiz by Remy Dulery brought lively discussion before the coffee break.
Mantle cell lymphoma and indolent lymphoma
Olivier Hermine started by highlighting how the prognosis of MCL drastically improved nowadays as compared to the years 1990. The standard of care with RCHOP/RDHAP/HDT/ASCT (with or without TBI) still leads to very good disease control and might even cure a subset of patients. Rituximab maintenance is also a part of the standard of care as shown in the Lyma 101 trial. Rituximab maintenance is also beneficial in elderly patients. Maintenance therapy might be more beneficial in patients who achieved MRD-negativity.
In second line the main revolution has been the BTK inhibitors including Ibrutinib, acalabrutinib and Zanubrutinib. After BTK failure, survival is poor. The options then include non-covalent BTK inhibitors such as pirtobrutinib, recently approved in this indication. Combinations such as Ibrutinib and venetoclax or Rituximab, ibrutinib and lenalidomide are currently explored inside clinical trials. Olivier Hermine also discussed the evidence to move the BTK inhibitors and/or lenalidomide to first line therapy.
Yasmina Serroukh discussed the place of CAR-T cell therapy, bispecific antibodies and allogeneic stem cell transplant on behalf of Tom Van Meerten. The main message is that these three modalities can lead to durable responses. However, allogeneic transplant is the only modality that has been proven curative with a long follow-up on large cohorts. The Zuma-2 data are compelling which led to approval of this product. EBMT incorporated CAR-T cell therapy as a standard of care for relapsed/refractory mantle cell lymphoma.
Chara Kyriakou discussed the Waldenstrom disease data. Autologous SCT is an option and outcome has not changed in the last two decades. Allogeneic SCT has been performed in 330 patients in the EBMT registry. It is still an option for selected patients refractory to BTK inhibitor and proteasome inhibitor. The data will be presented at ASH.
Tanya Freeman presented an interesting follicular lymphoma case. Silvia Montoto then gave an overview of the treatment landscape for follicular lymphoma, with a focus on autologous, allogeneic SCT and T cell engaging therapies. ASCT is particularly interesting in the subgroup of POD24 patients. CAR-T cell therapy is also active in transplant-exposed patients. There is insufficient data to guide decision on the exact sequence between the different modalities. However, ASTCT and EBMT provided a consensus stating that no cellular therapy should be offered in first line. In second line autologous SCT should be proposed in patients achieving CR or PR after salvage therapy, in particular for the POD24 subgroup; and CAR-T cell therapy for patients with stable or refractory disease. Allogeneic stem cell transplantation is still in the treatment landscape at 3rd line or later.
Hodgkin lymphoma
Aislin Barrett started with two illustrative cases of the issues faced by Hodgkin patients. Graham Collins then depicted the treatment of Hodgkin lymphoma with a focus on advanced stage. He delivered some important take home messages. Main outcome of RATHL is that bleomycin can be safely omitted after 2 cycles but overall the results were disappointing and long term PFS/OS are inferior as (indirectly) compared to other regimens. Procarbazine should be replaced by Dacarbazine according to an upcoming publication, mainly because of less gonadal toxicity. Doxorubicin increases breast cancer risk independently of radiotherapy. escBEACOPP should not be used in patients older than 60 years old and with caution in patients older than 50 years old with poor performance status and co-morbidities. After reviewing the three main current options, Graham Collins discussed the three new options that are BV-CHP according to the ECHELON-1 study , NIVO-AVD according to the S1826 trial and BreCADD. The audience was guided through the published outcome with details on the way to choose between these options.
Iman Abou Dalle presented the journey of a relapsed/refractory Hodgkin lymphoma patient.
Ali Bazarbachi then took the stage to discuss the strategies at relapse. The addition of a monoclonal antibody to a chemo backbone in 2nd line doubles the PET-negativity rate which is a major determinant of outcome. In second line ASCT is still standard of care. The overall survival of patients relapsing after ASCT has significantly improved the last decades. Checkpoint inhibitors used as monotherapy after ASCT have a high overall response rate but long lasting responses are mostly seen in patients achieving CR. Allogeneic SCT is safely feasible after checkpoint inhibitors and leads to durable responses and cure in a significant percentage of patients.
Carolina Arevalo presented a case of an 80 year old Hodgkin lymphoma patient. Graham Collins then concluded the session with a comprehensive talk on the management of Hodgkin lymphoma in the elderly, addressing the peculiarities of this population. Any lesion suspected of relapse should be biopsied as older patients also have an increased risk of other malignancies. Treatment should be adapted but there are proof of concept that we can efficiently treat elderly patients with Hodgkin. The most promising data are published with Nivo-AVD in a subgroup of the S1826 trial (50 patients in each arm, massive advantage for N-AVD as compared to BV-AVD).
Rare and niche entities
Pim Mutsaers discussed the management of PTLD. Definitions have been clarified in the WHO 2022 classification. Reduction of IS alone leads to 37% complete response but it should be early combined with Rituximab not to risk organ rejection and loss of function. Response-adapted treatment based on the Trappe study is standard of care in many centers. At relapse tabelecleucel allogeneic HLA 6/12 off the shelf EBV-specific T cells are registered and approved by EMA in this indication. ASCT leads to response in selected cases but with a high TRM. CAR-T cell therapy is feasible and safe in PTLD. A main take home message was that if the patients have a good organ function there is no reason to treat them differently, according to the histology.
Olivier Tournilhac discussed the definition of EATL and MEITL and showed the known and unknown aspects of treatment in first and subsequent lines of therapy. The role of ASCT is reasonably established in EATL but data on allo-sct are needed. For MEITL data are awaited in auto en alloSCT. Ongoing work within the EBMT registry will address these points.
Kate Cwynarski wrapped up the day by presenting a comprehensive update in primary CNS lymphoma. There are many options in the first line induction regimen and there are no comparative data. R-MTX is sufficient in combination with anti-retroviral therapy, ASCT is feasible but not needed due to different biology in HIV+ patients. HD MTX rechallenge in late relapse is part of the EORTC guidelines algorithm. Whole brain radiotherapy is associated with major toxicity and autologous stem cell transplantation has drastically improved the outcome in this disease.
PTCL
The session was divided in different parts. Norbert Schmitz started by presenting the standard treatment of PTCL with a focus on autologous and allogeneic stem cell transplantation. ALCL patients are the ones benefiting the most from etoposide (CHOEP). The ECHELON-1 study is the only positive study improving on CHOP in first line therapy. The role of autologous stem cell transplantation in first line for chemosensitive non ALK+ ALCL patients is supported by many retrospective series and an ongoing study will determine its place for patients in CR1 after induction. Allogeneic sct is a curative option with high overall survival for the patients that are able to get to transplant.
Kate Cwynarski took the stage to discuss the challenges and recent developments in cellular immunotherapy against T cell lymphoma. A recent accepted paper in Nature Medicine shows promising and durable responses with anti TBRC1 but the company stopped the development for this indication. Other potential targets are currently explored such as CD5, CD7, CD70 and CD30.
Fengrong Wang from China shared the experience of the largest transplant centre worldwide. T cel lymphoma patients with a high risk are treated upfront with an allogeneic sct using the Beijing protocol and a majority of haploidentical donors. The results are very encouraging with successful salvages even in high risk entities such as hepatosplenic T cell lymphoma.
Infections
For this year’s edition of the congress we had for the first time a session dedicated to the management of infection in B- (and T-) cel depleted patients. As this complication affects virtually all lymphoma patients treated with cellular therapy or chemoimmunotherapy, this topic was of high interest for the attendance. Sammy Huygens began with an overview of the prevention and therapeutic strategies against COVID-19 infections. He was followed by Virgil Dalm who wrapped the meeting up with a comprehensive talk on the management of acquired B cel deficiency whit antibiotics on demand, prophylactic. He presented the evidence and practical guidelines on IV immunoglobulins replacement.
Case presentations
We enjoyed interesting case presentations from Adrian Maraj, Emin Abdullayev, Evgenii Shumilov, Imke Karsten, Razvan Juganau and Igor Kos.
It was a successful meeting with 64 attendees from 17 countries. We look forward for the 2025 edition in Paris!