Konference: 2015 57th ASH Annual Meeting - účast ČR
Kategorie: Maligní lymfomy a leukémie
Téma: 623. Lymphoma: Chemotherapy, excluding Pre-Clinical Models: Poster III
Číslo abstraktu: 3941
Autoři: MD Stefanie Kreissl; Helen Goergen; MD Bastian von Tresckow; Dr. Karolin Behringer; Ing. Jana Marková; MD Andreas Lohri; Dr.med. Julia Meissner; Jose Zijlstra, MD; MD Richard Greil, Ph.D.; Prof. Dr. Max S Topp; M.D. Martin Soekler (Sökler); Prof. Dr. med. Hartmut Döhner (Doehner); MD Volker Diehl; Prof. MD Andreas Engert; MD Peter Borchmann, PhD
Methods: Patients aged between 18 and 60 years treated within the GHSG first-line trials HD13-HD15 were screened for primary progressive HL. Primary progression was defined as progressive disease during ongoing therapy, within 3 months after the end of treatment, or up to 6 months after the end of treatment in patients with partial response or stable disease in the final restaging. We investigated types and outcome of second-line treatment approaches and overall survival, which was calculated from first diagnosis of HL (OS) and from diagnosis of first progression or relapse (OSp).
Results: We analyzed 5,126 patients, of whom 112 (2.2%) were identified with primary progressive disease. Of those, 62 (55%) patients had initially been treated for advanced-stage HL with BEACOPP (bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone) variants, 30 (27%) for early-stage unfavorable HL with ABVD (doxorubicin, bleomycin, vinblastine, and dacarbazine)- or BEACOPP-like regimens (24 and 6 patients, respectively) and 20 (18%) for early–stage favorable HL with ABVD variants. The median age at the time of progression was 33 years.
3 patients (3%) died before a salvage therapy was started. Second-line treatment strategies included reinduction with intensified salvage regimens (77%), conventional chemotherapy (14%), and radiotherapy (8%). Autologous stem cell transplantation (ASCT) was performed in 76% of the patients who had received intensified reinduction chemotherapy, and allogeneic stem cell transplantation in ten (9%) patients. After the first salvage therapy, 42% of all patients achieved a complete remission (CR) and did not require further treatment. In total, 66% of the patient cohort achieved a CR after one or more second-line approaches. Median duration of the first CR was 61 months.
After a median observation time of 7 years, 55 of the patients with primary progressive disease (49%) had died, mostly from progressive or relapsed HL (n=36) or toxicity of salvage treatment (n=10). The majority of the 57 survivors was in CR at the time of analysis; 2 were under treatment for HL and there was no information available for one patient. Median OSp for the entire cohort was 83 months, 5-year OSp was 55.4% (95%-CI, 46% to 65%). Since OSp differed among patients of different initial stages and types of pre-treatment (early-stage favorable and unfavorable patients treated with ABVD variants, OSp 74.2% [61%-87%] vs. higher-stage patients treated with BEACOPP variants, OSp 42.9% [31% - 55%]), treatment groups were analyzed for survival separately. In both groups, patients responding to the first salvage therapy had a significantly better OSp compared to those not responding (each p<0.001). OS was significantly worse in patients with primary progressive disease when compared to the complementary study cohort in both treatment groups (each p<0.001). When comparing patients with primary progressive disease with those patients with a relapse of HL (n=272), there were significant advantages of the latter regarding OS and OSp within the BEACOPP-pre-treated subgroup (each p<0.001). In patients pre-treated with ABVD variants, there was also a significant difference in OS (p=0.007), but no detectable difference regarding OSp (5-year OSp 74% vs. 78%, p=0.3).
Conclusion: Overall, the 5-year OSp in this unselected patient cohort of primary progressive HL patients is encouraging and supports the use of aggressive salvage regimens and consolidating high-dose chemotherapy in general. However, this approach is known to induce severe long-term toxicities and has limited efficacy in patients failing first-line treatment for advanced stage disease. We conclude that there is a need to develop different treatment approaches in primary progressive HL patients.
Disclosures: von Tresckow: Novartis: Consultancy , Other: Travel and accomodation , Research Funding ;Amgen: Other: honoraria for preparation of scientific educational events ; Celgene: Other: honoraria for preparation of scientific educational events ; Takeda: Consultancy . Zijlstra: Roche: Consultancy , Research Funding ; Gilead: Consultancy . Topp: Astra: Consultancy ; Regeneron: Consultancy ; Affimed: Consultancy , Research Funding ; Roche: Consultancy , Other: Travel Support ; Jazz: Consultancy ; Pfizer: Consultancy ;Amgen: Consultancy , Honoraria , Other: Travel Support . Engert: Takeda: Consultancy , Research Funding .Borchmann: Millennium: Research Funding.
Datum přednesení příspěvku: 7. 12. 2015