Gastrale MALT-Lymphome – von pathogenetischen Erkenntnissen zu konsequenter Deeskalation der Therapie

ZusammenfassungDas gastrale MALT (mucosa-associated-lymphoid-tissue) -Lymphom ist das häufigste gastrointestinale Lymphom. Über Jahrzehnte hinweg galten zunächst die Operation und später Bestrahlung und Chemotherapie als etablierte Therapiestandards. Vor etwa 30 Jahren wurde die pathogenetische Bedeutung der Helicobacter-pylori-Infektion für die Entstehung des gastralen MALT-Lymphoms deutlich. In den folgenden Jahren wurden die pathogenetischen Erkenntnisse konsequent in die klinische Medizin umgesetzt. Dies hat zu einer radikalen Änderung der Therapie dieser Lymphome geführt. Heute ist international die Helicobacter-pylori-Eradikation als Therapie der ersten Wahl anerkannt. Sie führt in den meisten Fällen zu einer Lymphomregression. Die Langzeitprognose der Patienten nach alleiniger Eradikationsbehandlung ist exzellent, selbst dann, wenn endoskopische und/oder histologische Residuen bestehen bleiben und eine „Watch-and-wait“-Strategie gewählt wird.Die pathogenetischen Erkenntnisse und ihre klinische Anwendung haben zu einer konsequenten Therapiedeeskalation bei den gastralen MALT-Lymphomen geführt. Die vorliegende Übersicht zeigt die einzelnen Schritte dieser Entwicklung und gibt eine Empfehlung zum aktuellen Management von Patienten mit gastralen MALT-Lymphomen.

Venetoclax Combined with Dose-Adjusted R-EPOCH (VR-DA-EPOCH) As Treatment of Richter's Syndrome: A Real-World Study

Background: To evaluate the efficacy and safety of venetoclax, rituximab plus dose-adjusted etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin (VR-DA-EPOCH) in Richter's syndrome (RS), we conducted a single-arm, retrospective, observational, real-world study in our center. Methods: Patients who had history of CLL/SLL were diagnosed as RS by biopsy during treatment or watch and wait strategy. VR-DA-EPOCH was given as follow, venetoclax was administered with accelerated ramp-up from 20 mg per day to 400 mg per day, d1-10 during cycle 1, 400 mg daily on day1-10 of cycle 2-6, rituximab 375 mg/m 2 on day 0 of cycle 1 and 500 mg/m 2 on day 0 of cycle 2-6, plus etoposide (50 mg/m 2,day1-4), vincristine (0.4 mg/m 2 day 1-4) or vindesine 3 mg/m 2 day 1 , doxorubicin (10 mg/m 2 day 1-4), prednisone (60 mg/m 2, day 1-5), cyclophosphamide (750 mg/m 2 day 5), 21 days per cycle，dose adjustment on the basis of nadir ANC and platelet count are as previously reported by Wison WH. Response assessment was conducted after 2 or 3 cycles by enhanced CT or PET/CT and after 6 cycles (EOT) by PET/CT according to 2014 Lugano criteria. Minimal residual disease (MRD) of CLL cell in peripheral blood (PB) and bone marrow (BM) was detected after 2 or 3 and 6 cycles by flow cytometry. uMRD was defined as less than 1 CLL cell per 10 4 leukocytes. Results: 7 RS patients were enrolled in Pukou CLL Center from 10/2019 to 7/2021 and the last follow up was 07/25/2021. The median age was 52 years old. Unmutated IGHV, complex karyotype (CK) and TP53 deletion and/or mutation was detected in 100% (6/6), 20% (1/5) and 40% (2/5) patients, respectively. 5 patients received at least one prior line (range: 1-5) treatment for CLL/SLL, with 4 patients received ibrutinib as last prior therapy and one patient previously exposed to venetoclax. 2 patients were diagnosed as RS during watch and wait. The median duration from diagnoses or previous treatment for CLL/SLL to RS was 12 months (range: 3-14). All patients underwent lymph node (n=6) or bone biopsy(n=1) at the site of SUVmax or secondary SUV uptake (unaccessible for SUVmax) by PET/CT and was confirmed as transformed to non-GCB type of diffuse large B-cell lymphoma (DLBCL). Furthermore, 4 of 4 (100%) available patients were confirmed as clonal-related RS by detecting IGHV gene usage. 3 patients acquired CK, and 2 patients appeared BTK C481S mutation. 7 patients completed at least 2 cycles and were available for efficacy and safety assessment. Overall response rate (ORR) was 100% after 2 or 3 cycles, and CR rate (CRR) was 60% after 6 cycles in 5 patients who completed 6 cycles. 2 patients experience disease progression (PD) after cycle 2 and cycle 4 respectively, with one ceased after the addition of brentuximab and the other received CD20 UCAR-T and progressed 3 months later, transit to allo-hemapoietic stem cell transplant (allo-HCT). One patient received auto-hemapoietic stem cell transplant (auto-HCT) and CD19-CAR-T as consolidation and remains in CR, one patient experience PD after 6 cycles and attained CR with chidamide , programmed death-1 (PD-1) inhibitor Sintilimab and XPO1 inhibitor Selinexor, bridging to allo-HCT and remains in CR. Another patient who achieved CR after 6 cycles progressed 6 months later and ceased within one month. 2 patients transformed without previous treatment wait for final evaluation. 60% (3/5) patients attained MRD negativity both in the PB and BM after 6 cycles. The median tolerable dose was 60% (50%-70%) of standard EPOCH and the median dose of venetoclax was 400mg daily for 7 days each cycle. No tumor lysis syndrome (TLS) happened during venetoclax ramp-up. The most common grade 3 or 4 adverse effects (AEs) was agranulocytic fever (6/7, 85.7%), thrombocytopenia (3/7, 42.9%) and sepsis (2/7, 28.6%). 3 (42.9%) patients discontinued venetoclax due to severe AEs and the median duration of discontinuation was 3 days. 85.7% (6/7) had venetoclax dose reduction or interruption due to grade 3 or 4 neutropenia. Conclusion: VR-DA-EPOCH showed high response rate, impressive CR with uMRD and manageable toxicity in patients with RS, even with previous exposure to new target drugs. VR-DA-EPOCH could be recommended as an effective treatment choice for RS, CAR-T or allo-HCT should be considered as subsequent strategy for long term disease control. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

Assessment of Quality of Life in Chinese Patients with Chronic Lymphocytic Leukemia

Background: Despite the changing landscape of treatment of chronic lymphoma leukemia (CLL) and in contrast to the large number of quality of life (QoL) and psychosocial studies in patients with solid tumors, relatively few studies have reported QoL in patients with CLL. This study aims to assess depression, anxiety, stress and QoL in a Chinese CLL cohort. Patients and Methods: Taking advantage of the European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30 accompanying CLL-specific module QLQ-CLL17 questionnaire and DASS-21 questionnaire, a total of 50 Chinese patients with CLL completed self-reported questionnaires from December 2019 to July 2021, assessing the level of depression, anxiety, stress and QoL. Results: Among the 50 CLL patients, 34 patients were male. The median age was 57 (22-77) years old. 66% of the patients were uncertain about the staging of the disease. 36% of the patients were uncertain about therapeutic implications of CLL. According to EORTC QLQ-C30, patients had low level of physical functioning, role functioning, emotional functioning, cognitive functioning and social functioning were 80%, 32%, 68%, 66%, 64%, respectively. Patients in active-treatment group had significantly lower level of physical function than "watch and wait" group (90% vs. 65%, P=0.03). The proportion of patients with cognitive problems was significantly higher in female patients than in male patients (93.8% vs. 52.9%, P=0.004). According to QLQ-CLL17, patients with symptom burden, physical condition and worries about health were 94% (47/50), 86% (43/50), 98% (48/50). Patients under 60 years old had higher scores for worries about health than patients older than 60. According to DASS-21 questionnaire, 86% of the patients had depression symptomatic scores (mild grade: 2%, medium grade: 52%, severe grade: 20%, very severe grade: 12%). 84% of the patients had anxiety symptomatic scores ( mild grade: 6%, medium grade: 14%, severe grade: 30%, very severe grade: 34%). 64% of the patients had stress symptomatic scores ( mild grade: 18%, medium grade: 22%, severe grade: 16%, very severe grade: 8%). And these psychosocial issues had no significant correlation with gender, age, household income and treatment . The same questionnaires were completed by 5 patients for the second time after median 8（2-18）months. Compared to the initial assessment, they scored significantly worse on the emotional scales (P=0.0237). No significant difference regarding physical functioning, role functioning, cognitive functioning and social functioning were observed between the former and the latter. Conclusions: The majority of CLL patients had impaired QoL and psychosocial issues. Active-treatment patients had worse physical condition than "watch and wait" patients. Male patients had better cognitive functioning. Younger patients had more worries about health than the elderly. Greater efforts should be made in management of CLL patients. Disclosures No relevant conflicts of interest to declare.