Cycles Of Rituximab Research Articles

Blastic plasmacytoid dendritic cell neoplasm: challenges in diagnosis and treatment with potential of venetoclax as an alternative to vincristine in high-risk patients—a case report

BackgroundBlastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare and challenging cancer for diagnosis and treatment. Accurate diagnosis plays a crucial role guiding appropriate treatment, typically involving high-intensity lymphoblastic leukemia regimens which typically include vincristine. However, the use of vincristine may be particularly limited in patients with pre-existing neuropathy or individuals at high risk of developing it. Here, we present a case of BPDCN that was initially diagnosed as marginal zone lymphoma (MZL) and subsequently as non-specific T-cell lymphoma, thus highlights the importance of accurate diagnosis and modified treatment.Case presentationA 49-year-old Arab man with a medical history of diabetes, peripheral neuropathy, hypertension, and depression presented with widespread, painless multiple skin lesions. After undergoing a biopsy at another institution, the patient was initially diagnosed with MZL, and received two cycles of bendamustine and rituximab. However, the disease relapsed and was later diagnosed with non-specific T-cell lymphoma, which proved refractory to a single cycle of CHOP chemotherapy. The patient was subsequently referred to our centre, where a comprehensive evaluation revealed BPDCN with a unique finding on bone marrow exam: signet ring plasmacytoid dendritic cells. Due to the patient's pre-existing neuropathy and previous treatment, we administered the Hyper-CVAD regimen with a 50% reduction in vincristine dosage, which resulted in an excellent response. During the second part of cycle one, when new skin lesions started appearing, venetoclax was added to the treatment regimen. Subsequently, we discontinued vincristine due to worsening neuropathic pain and neuropathy-related weakness. Venetoclax was continued in cycle two and led to a complete response. The patient achieved a disease-free state for the first time in disease course, maintaining it for a period of over six weeks before experiencing a relapse.ConclusionsAccurate diagnosis is crucial for guiding appropriate treatment. Our case highlights the challenges associated with diagnosis and treatment, as well as the potential of venetoclax as an alternative to vincristine, particularly in patients with pre-existing neuropathy or those at a high risk of developing it. Further research is needed to evaluate the effectiveness of BCL2 inhibitors as a replacement for essential drugs and its potential as a bridging therapy until patients can undergo a stem cell transplant.

Positron emission tomography-adapted therapy in low-risk diffuse large B-cell lymphoma: results of a randomized, phase III, non-inferiority trial.

The current standard of care for non-bulky diffuse large B-cell lymphoma (DLBCL) patients with an International Prognostic Index (IPI) of 0 is four cycles of rituximab plus cyclophosphamide, doxorubicin, vincristine and prednisone (R-CHOP) but whether the same efficacy can be achieved with reduced chemotherapy regimen of four cycles for non-bulky DLBCL patients with an IPI of 1 remains unclear. This study compared four cycles versus six cycles of chemotherapy in non-bulky low-risk DLBCL patients with negative interim positron emission tomography with computed tomography (PET-CT, Deauville 1-3), irrespective of age and other IPI risk factors (IPI 0-1). This was an open-label, randomized, phase III, non-inferiority trial. Patients aged 14-75 years with newly diagnosed low-risk DLBCL, according to IPI, achieving PET-CT confirmed complete response (CR) after four cycles of R-CHOP were randomized (1:1) between four cycles of rituximab (4R-CHOP+4R arm) or two cycles of R-CHOP plus two cycles of rituximab (6R-CHOP+2R arm). The primary endpoint was 2-year progression-free survival (PFS), conducted in the intention-to-treat population. Safety was assessed in patients with at least one cycle of assigned treatment. The non-inferiority margin was -8%. A total of 287 patients were included in the intention-to-treat analysis, the median follow-up was 47.3 months, and the 2-year PFS rate was 95% (95% confidence interval [CI], 92% to 99%) and 94% (95% CI, 91% to 98%) for the 4R-CHOP+4R and 6R-CHOP+2R arm. The absolute difference in 2-year PFS between the two arms was 1% (95% CI, -5% to 7%), supporting the non-inferiority of 4R-CHOP+4R. Grade 3-4 neutropenia was lower in the last four cycles of rituximab alone in the 4R-CHOP+4R arm (16.7% versus 76.9%), with decreased risk of febrile neutropenia (0.0% versus 8.4%) and infection (2.1% versus 14.0%). For newly diagnosed low-risk DLBCL patients, interim PET-CT after four cycles of R-CHOP was effective in identifying patients with Deauville 1-3 who would have a good response and Deauville 4-5 patients who might have high-risk biological features or develop resistance. Reducing the standard six cycles to four cycles of chemotherapy had comparable clinical efficacy and fewer adverse events in low-risk, non-bulky DLBCL with interim PET-CT confirmed CR.

BI11 Cutaneous presentation of Kaposi sarcoma following allogeneic haematopoietic stem cell transplantation for myeloma

Abstract Iatrogenic Kaposi sarcoma (KS) is a relatively frequent occurrence following solid-organ transplants (0–5%), in part due to prolonged immunosuppression. However, its occurrence after haematopoietic stem cell transplantation (HSCT) is rare, with only 15 cases described in the literature. We report a case of KS presenting in the skin of a patient who had received a matched unrelated donor allogeneic HSCT for IgG kappa myeloma. A 55-year-old HIV-negative white man with myeloma underwent an allogeneic HSCT from a matched, unrelated donor following conditioning chemotherapy with fludarabine–melphalan and antithymocyte globulin. Post-transplant, he was maintained on ciclosporin as graft-versus-host disease (GVHD) prophylaxis. On day 14 post-transplant, he developed a widespread eczematous eruption that rapidly evolved into an erythroderma; a skin biopsy was consistent with acute GVHD. He was managed with superpotent topical steroids and a 5-day course of oral prednisolone. He began extracorporeal photopheresis (ECP) on day 33 post-transplant, having failed to respond adequately to systemic steroids. He also completed four cycles of rituximab. Ciclosporin was stopped by day 130 post-transplant. He had completed 14 cycles of ECP by day 139 post-transplant, with resolution of cutaneous GVHD; however, he had developed a rapidly growing solitary dusky-red nodule on his right neck that was excised due to diagnostic uncertainty. Histology revealed a dermal haemorrhagic exophytic vascular tumour composed of lobules and sheets of epithelioid cells with an eosinophilic cytoplasm and pleomorphic nuclei. Immunoperoxidase staining was negative for S100, MNF-116 and AE1/AE3. The same cells were strongly and diffusely positive for the vascular markers CD31, CD34 and ERG. The lesional cells were positive for human herpesvirus (HHV)-8 confirming a diagnosis of Kaposi sarcoma. He subsequently developed a second lesion on his left forearm, despite being off all immunosuppression. A repeat bone biopsy confirmed that he remains in morphological remission from his myeloma. Positron emission tomography–computed tomography has not identified extracutaneous disease. KS following HSCT is rare, but it can be fatal. Skin lesions are the dominant clinical presentation. HHV-8 has an important role in the pathogenesis, and transplant-related KS may occur secondary to reactivation of the virus as a result of significant immunosuppression following HSCT. However, it could also occur as primary infection or be transmitted with donor cells. The outcome of KS after HSCT is variable. A watch and wait strategy can be applied if immune recovery is expected. In our patient, it developed 5 months after HSCT; shortly after immunosuppression had been tapered, he remains well and will be closely monitored for further suspicious lesions.

Rituximab plus multiagent chemotherapy for newly diagnosed CD20-positive acute lymphoblastic leukemia: a prospective phase II study.

We performed a prospective study to determine the efficacy and safety of rituximab including chemotherapy in CD20-positive acute lymphoblastic leukemia (ALL). Patients with newly diagnosed ALL, aged ≥ 15 years, were eligible for the study if their leukemic blast cells in bone marrow expressed CD20 ≥ 20% at the time of diagnosis. Patients received multiagent chemotherapy with rituximab. After achieving complete remission (CR), patients received five cycles of consolidation with concomitant rituximab. Rituximab was administered monthly from day 90 of transplantation for patients who received allogeneic hematopoietic cell transplantation. In patients with Philadelphia (Ph)-negative ALL, 39 of 41 achieved CR (95.1%), the 2- and 4-year relapse-free survival (RFS) rates were 50.4% and 35.7%, and the 2- and 4-year overall survival (OS) rates were 51.5% and 43.2%, respectively. In the group with Ph-positive ALL, all 32 patients achieved CR, the 2- and 4-year RFS rates were 60.7% and 52.1%, and the 2- and 4-year OS rates were 73.3% and 52.3%, respectively. In the Ph-negative ALL group, patients with higher CD20 positivity experienced more favorable RFS (p < 0.001) and OS (p = 0.06) than those with lower CD20 positivity. Patients who received ≥ 2 cycles of rituximab after transplantation had significantly improved RFS (hazard ratio [HR], 0.31; p = 0.049) and OS (HR, 0.29; p = 0.021) compared with those who received < 2 cycles. The addition of rituximab to conventional chemotherapy for CD20-positive ALL is effective and tolerable (Clinicaltrials. gov NCT01429610).

Cotrimoxazole as a Preventative Intervention for Pneumocystis Pneumonia in Pemphigus Patients Treated with Rituximab: A Retrospective Study.

Pneumocystis jirovecii pneumonia (PJP) is a severe, life-threatening complication in patients treated with rituximab. However, there is no consensus on the primary prophylaxis for it in rituximab-treated pemphigus patients. Therefore, we sought to investigate the prophylactic efficacy and safety profile of cotrimoxazole for reducing the risk of developing PJP in pemphigus patients receiving rituximab. This single-center retrospective study investigated 148 pemphigus patients undergoing a first cycle of rituximab between 2008 and 2021 at a tertiary referral center in northern Taiwan. Patients were divided into the prophylaxis group (N = 113) and the control group (N = 35) according to whether or not cotrimoxazole was administered. The primary outcome was the 1-year incidence of PJP in the two groups, while the secondary outcome was the incidence of cotrimoxazole-related adverse events. Of the 148 patients enrolled in this study, three patients, all in the control group, developed PJP during the 1-year follow-up. The incidence of PJP (8.6%) in the control group was significantly higher than that in the prophylaxis group (0%) (p = 0.012). The incidence of cotrimoxazole-related adverse events was 2.7%, and none of the cases were associated with life-threatening conditions. In addition, the cumulative prednisolone dose was associated with a trend of a higher risk of PJP (p = 0.0483). Prophylactic cotrimoxazole significantly reduces the risk of PJP in a certain high-risk population and has a tolerable safety profile.

#6333 LARGE B CELL RENAL INFILTRATION IN A PATIENT WITH WALDESTRöM MACROGLOBULINEMIA: A CASE REPORT

Abstract Background and Aims Waldeström Macroglobulinemia (WM) is a clinicopathologic entity demonstrating lymphoplasmacytic lymphoma (LPL) in the bone marrow with an IgM monoclonal gammopathy in the blood. Only 15% of patients with WM may develop a renal insufficiency due to either glomerular or tubulointerstitial pathologies. Most common findings include deposits of IgM in the glomerular basement membrane and infiltration of lymphocytes or plasmacytoid cells; light chain cast nephropathy; nephrotic syndrome led by AL amyloid deposition; immune-mediated glomerulonephritis (typically due to IgM deposition or cryoglobulinemia) and non-amyloid nephrotic syndrome (minimal change-like). Moreover, WM may evolve in hematological malignancies with renal localization. Therefore, a renal biopsy may be needed in patients who have recent unexplained renal dysfunction. Method A 72-year-old male with a history of WM is referred to our nephrology center for declining renal function. He had been diagnosed with Waldeström Macroglobulinemia IgM Kappa 4 years prior to presentation, at onset serum protein electrophoresis showed an M spike of 4900. After diagnosis confirmation, he underwent treatment with 6 cycles of rituximab and bendamustine resulting in a complete response and M spike at serum protein electrophoresis lowering to 23. At WM diagnosis his renal function was normal, he had no proteinuria nor urinary Bence-Jones. His medical background also included hypertension and diabetes mellitus type 2, both in good pharmacologic control and Sars-Cov2 infection. Two years later, we witnessed to progressive presentation of anemia, fatigue and cough along with hepatomegaly, axillary lymphomegaly, pulmonary basal thickenings and IgM levels elevation. Serum creatinine was 1,47 mg/dl, proteinuria 1,75 g/die, no urinary Bence-Jones proteinuria. A renal ultrasound showed poor cortico-medullary differentiation in both kidneys and a left kidney slightly bigger than the other one. Respiratory symptoms and pulmonary thickenings persisted after antibiotics therapy, also cytology and culturing exams performed on broncho-alveolar lavage resulted negative. To exclude a possible relapse of WM, a BOM and a lymphnodal mass biopsy were performed. Both exams showed no disease progression. Due to lack of WM progression, the patient is referred to renal biopsy execution. Results Renal biopsy showed morpho-phenotypic findings for localization of mainly large B peripherical cells, partial plasmocytic differentiation and high proliferation levels. Further exams revealed a double monoclonal component IgM Kappa with normal Kappa/Lambda, also a total Body TC was performed, and it evidenced a possible renal and pulmonary lymphoproliferative disease involvement. In the figure an image of the patient's renal biopsy showing IgM immunofluorescence. Our patient is still fulfilling all the supplementary analysis needed to evaluate the best therapeutic strategies. We also reviewed all renal biopsies performed in our center in patients with hematological diseases in the last 10 years and a neoplastic renal infiltration was documented in just 6 cases out of 650 biopsies. Conclusion Although lymphomatous infiltration of the kidney in WM is a rare event, it should be considered in patients presenting with abnormal renal function. It is important during follow-up to monitor kidney function in patients with plasma cell dyscrasias, even if patients appear to have stable lymphoproliferative disease.

17th International Conference on Malignant Lymphoma, Palazzo dei Congressi, Lugano, Switzerland, 13 - 17 June, 2023.

Introduction: The optimal treatment for very elderly patients (pts) with newly diagnosed Diffuse Large B Cell Lymphoma (DLBCL) remains controversial. R-mini-CHOP is an established standard of care in elderly patients with DLBCL, with a 2 yr OS of 59% and PFS of 47% (Peyrade et al., Lancet Oncol 2011). We present our final data from this prospective Phase II study of ibrutinib, rituximab and mini-CHOP in pts ≥75 yrs with newly diagnosed DLBCL. Methods: Pts received six 21-day cycles of ibrutinib 560 mg daily and R-mini-CHOP (Rituximab 375 mg/m2, cyclophosphamide 400 mg/m2, doxorubicin 25 mg/m2, vincristine 1 mg on day 1 & prednisone 40 mg/m2 or 100 mg/d × 5) followed by an additional two 21 day cycles of rituximab + ibrutinib (or high dose methotrexate for CNS prophylaxis). Primary endpoints were deliverability and 2 year overall survival (OS). Sample size calculations were made using a one-sample two-sided approach to detect a 15% improvement on the fixed Peyrade reference OS (59%) and PFS (47%) rates. Results: Eighty pts were recruited from Nov 2015 to Nov 2018. One died prior to receiving treatment and is not included in the analysis. Median age was 82 yrs (75–95); 81% stage III/IV; 54% age adjusted IPI 2–3. With a median follow-up of 35.5 months (m) (0.2, 71.7) (data cut 6 September 2022), there was a non-significant trend towards improvement in 2-year OS of 68% (55.6%, 77.4%) compared to the reference Peyrade cohort of 59% (p = 0.11). Median OS was 72 m (95% CI 35 m to not reached (NR)). Median 2-year PFS of 60.0% (47.7%, 70.3%) was significantly improved compared to the reference cohort of 47% (p = 0.03), with a median PFS of 40 m (95% CI 20.41, NR). Overall response assessment assessed by investigators at the end of treatment was 76% (61/80 pts), with a complete response rate of 70% (56/80 pts). All 6 cycles of R-mini-CHOP were completed in 63/79 pts (80%) and 57/79 pts (71%) completed all 8 cycles of therapy. The median Average Relative Total Dose and Average Relative Dose Intensity for the entire regimen was 97% (IQR 82, 100; 88, 100). 34/79 pts (43%) have died, 17 due to progressive disease and 5 were treatment-related. 67% pts experienced an SAE. Most common AEs were infections and diarrhoea (majority grade 1–2). In the EORTC QLQ-C30 there was an improvement in functional and symptom scales and on the EQ-5D-5L survey, there was a significant improvement in the median health state classification score and median visual analogue scale thermometer score over time. Encore Abstract - previously submitted to EHA 2023 The research was funded by: Janssen-Cilag Pty Ltd. Keywords: Aggressive B-cell non-Hodgkin lymphoma, Combination Therapies Conflicts of interests pertinent to the abstract. E. Verner Research funding: Janssen-Cilag Pty Ltd. E. Hawkes Consultant or advisory role: Janssen-Cilag Pty Ltd. T. Cochrane Consultant or advisory role: Janssen Cilag Pty Ltd. C. Y. Cheah Consultant or advisory role: Janssen-Cilag Pty Ltd. Honoraria: Janssen-Cilag Pty Ltd. M. K. Gandhi Research funding: Janssen-Cilag Pty Ltd. B. E. Butcher Other remuneration: Janssen Cilag Pty Ltd. J. Trotman Research funding: Janssen-Cilag Pty Ltd.

Subgroup analysis of elderly patients (pts) with diffuse large B-cell lymphoma (DLBCL) in the phase 3 POLARIX study.

7518 Background: In the Phase 3 POLARIX study (NCT03274492), polatuzumab vedotin with rituximab, cyclophosphamide, doxorubicin, and prednisone (Pola-R-CHP) significantly improved progression-free survival (PFS) compared with rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone (R-CHOP), with a similar safety profile in pts aged 18–80 years with previously untreated DLBCL (Tilly et al. 2022). Combination regimens may be associated with higher rates of toxicity in elderly pts. We report the efficacy and safety of Pola-R-CHP vs R-CHOP in pts aged ≥70 years enrolled in POLARIX. Methods: POLARIX methods were described by Tilly et al. (2022). Pts with previously untreated DLBCL were randomized 1:1 to receive 6 cycles of Pola-R-CHP or R-CHOP, plus 2 cycles of rituximab. This analysis focused on pts aged ≥70 years at enrollment. Results: Overall, 284 pts were analyzed for efficacy (Pola-R-CHP, n=141; R-CHOP, n=143) and 280 pts were analyzed for safety (Pola-R-CHP, n=137; R-CHOP, n=143). Median age was 74 years (range 70–80), and 69.7% had an International Prognostic Index score of 3–5. Most pts in either arm received all 6 doses of polatuzumab vedotin or vincristine (88.3% and 91.6% in the Pola-R-CHP and R-CHOP arms, respectively). At data cutoff (June 28, 2021; median follow-up: 24.2 months), the risk of progression, relapse or death was lower with Pola-R-CHP vs R-CHOP (hazard ratio [HR] 0.64; 95% confidence interval [CI]: 0.41–0.99) (Table). Death by any cause occurred in 14.2% and 19.6% of pts treated with Pola-R-CHP and R-CHOP, respectively. Overall survival (OS) and disease-free survival (DFS) results are presented in the Table. Safety profiles were generally comparable for Pola-R-CHP vs R-CHOP, including rates of Grade 3–5 adverse events (AEs), Grade 5 AEs, serious AEs, peripheral neuropathy (any grade), neutropenia (Grade 3–4), and infection (Grade 3–4) (Table). Conclusions: Pola-R-CHP and R-CHOP demonstrated similar safety profiles in pts aged ≥70 years with previously untreated DLBCL. The risk-benefit profile favored Pola-R-CHP vs R-CHOP. Clinical trial information: NCT03274492 . [Table: see text]

Phase 3 trial of subcutaneous epcoritamab + R-CHOP versus R-CHOP in patients (pts) with newly diagnosed diffuse large B-cell lymphoma (DLBCL): EPCORE DLBCL-2.

TPS7592 Background: In pts with newly diagnosed DLBCL, standard treatment with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) has a 5-year progression-free survival (PFS) rate of 67.0%, 58.4%, and 45.8% for International Prognostic Index (IPI) 2, 3, and 4–5, respectively (Ruppert et al, Blood 2020). Epcoritamab is a subcutaneously administered, bispecific antibody that binds CD3 on T cells and CD20 on B cells, inducing potent and selective T-cell–mediated killing of malignant CD20+ B cells (Hutchings et al, Lancet 2021). Epcoritamab monotherapy demonstrated deep and durable responses (overall response rate [ORR], 63%; complete response rate, 39%) and was generally well tolerated in pts with relapsed/refractory (R/R) aggressive, large B-cell lymphoma (LBCL) (Thieblemont et al, J Clin Oncol 2022). Results from an ongoing phase 1/2 study in high-risk pts with newly diagnosed DLBCL (EPCORE NHL-2 arm 1; NCT04663347) show that epcoritamab + R-CHOP has promising efficacy and a manageable safety profile in high-risk pts with IPI 3–5. Among efficacy-evaluable pts (n = 31), ORR was 100% and complete metabolic response (CMR) was 77%; cytokine release syndrome (CRS) events (n = 17/33; 52%) were mostly low-grade, had predictable timing, and did not lead to treatment discontinuation (Falchi et al, ASCO 2022, abstract 7523). These encouraging data support further evaluation of epcoritamab + R-CHOP for the treatment of newly diagnosed DLBCL. Methods: This phase 3, global, multicenter, open-label study (NCT05578976) evaluates the efficacy and safety of epcoritamab + R-CHOP in adults newly diagnosed with one of the following CD20+ DLBCL (de novo or transformed from follicular lymphoma [FL]): 1) DLBCL, not otherwise specified (NOS); 2) high-grade B-cell lymphoma with MYC and BCL-2 and/or BCL-6 rearrangement; 3) T-cell/histiocyte–rich LBCL; 4) Epstein-Barr virus–positive DLBCL, NOS; or 5) FL grade 3b. Other key eligibility criteria include IPI ≥2 (pts with IPI 2 not to exceed ~30% of total pts), ECOG PS 0–2, and ≥1 measurable disease site. Approximately 900 pts will be randomized 2:1 to either epcoritamab + R-CHOP (6 cycles, followed by 2 cycles of epcoritamab) or R-CHOP (6 cycles, followed by 2 cycles of rituximab). The primary efficacy endpoint is PFS in pts with IPI 3–5 (based on IRC assessment per Lugano criteria). The secondary efficacy endpoints are PFS in pts with IPI 2–5, event-free survival, CMR, overall survival, and minimal residual disease negativity. Safety endpoints include incidence and severity of treatment-emergent adverse events (AEs), serious AEs, and AEs of special interest (CRS, immune cell–associated neurotoxicity syndrome, and clinical tumor lysis syndrome. Enrollment began in January 2023 globally. Clinical trial information: NCT04663347 , NCT05578976 .

FIVE‐YEAR RESULTS OF A PHASE 2 STUDY OF CNS‐ORIENTED THERAPY WITH R‐CHOP FOR UNTREATED INTRAVASCULAR LARGE B‐CELL LYMPHOMA: FINAL ANALYSIS OF THE PRIMEUR‐IVL STUDY

Introduction: Intravascular large B-cell lymphoma (IVLBCL) is a rare disease entity of extranodal large B-cell lymphoma characterized by selective growth of lymphoma cells in the lumina of small vessels. The prognosis of IVLBCL is typically poor without timely diagnosis. Based on the promising efficacy of rituximab-containing chemotherapy and a high incidence of secondary central nervous system (CNS) involvement after rituximab-chemotherapy, we conducted the PRIMEUR-IVL study to explore the efficacy of CNS-oriented therapy with rituximab-chemotherapy whose primary analysis demonstrated 2-year progression-free survival (PFS) of 76% and 2-year overall survival (OS) of 92% with a low incidence of secondary CNS involvement of 3%. Patients and Methods: The PRIMEUR-IVL study is a multicenter, single-arm, phase 2 trial at 22 hospitals in Japan for untreated histologically confirmed IVLBCL patients without apparent CNS involvement at diagnosis. The treatment regimen includes three cycles of R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone) followed by two cycles of rituximab with high-dose methotrexate and additional three cycles of R-CHOP. Intrathecal chemotherapy including methotrexate, cytarabine, and prednisolone was administered four times during the R-CHOP phase. We present a preplanned final analysis of the PRIMEUR-IVL study including 5-year PFS, OS and secondary CNS involvement. Results: A total of 38 patients were enrolled, of whom 37 patients were eligible. One patient with a history of testicular lymphoma was excluded. As of July 2021, with a median follow-up of 7.1 years (interquartile range 5.6–8.7), 5-year PFS in all eligible patients was 68% (95% confidence interval [CI] 50%–80%) and OS was 78% (95% CI 61%–89%). Median PFS and OS were not reached. No additional secondary CNS involvement was observed after primary analysis with 3% of cumulative incidence. Severe adverse events after the primary analysis were grade 4 neutropenia (n = 1) and grade 4 myelodysplastic syndrome that did not require specific treatment (n = 1). During the observation period after enrollment, there were a total of eight deaths due to following reasons: primary disease (n = 6), sepsis (n = 1), and unknown sudden death (n = 1). Conclusions: In this 5-year, long-term follow-up analysis of the PRIMEUR-IVL study, frontline treatment of CNS-oriented therapy with standard R-CHOP for untreated IVLBCL patients without apparent CNS involvement provided durable response and clinically meaningful results for PFS, OS, and low incidence of secondary CNS involvement with manageable toxicity. Our result provides one of active treatment for untreated IVLBCL patients. The research was funded by: The Practical Research for Innovative Cancer Control, the Japan Agency for Medical Research and Development (AMED), Japan, JP19ck0106511 and the National Cancer Center Research and Development Fund, 23-A-17 and 26-A-4. The research was supported by the Center for Supporting Hematology-Oncology Trials (C-SHOT). Keyword: chemotherapy Conflicts of interests pertinent to the abstract K. Shimada Honoraria: AstraZeneca, Chugai, Eisai, Kyowa Kirin, Symbio M. Yamaguchi Honoraria: AbbVie, Bristol Myers Squibb, Chugai, Janssen, Kyowa Kirin, Meiji Seika, MSD, Nippon Shinyaku, SymBio, Takeda Research funding: AstraZeneca, Chugai Pharma, Genmab, Incyte, Eisai, Takeda, Nippon Shinyaku, Otsuka, Asahi Kasei, Kyowa Kirin, Chugai H. Nagai Honoraria: Kyowa Kirin, Takeda, Chugai, Bristol Myers Squibb, Eisai, Novartis, Janssen, Mundi Pharma, Lilly, AstraZeneca, Ono, Meiji, AbbVie, Nippon Shinyaku, GSK, Sumitomo Pharma, Genmab, CSL Behring Research funding: Kyowa Kirin, Takeda, Chugai, Bristol Myers Squibb, Janssen, AstraZeneca, Ono, AbbVie, Nippon Shinyaku, Daiichi-Sankyo, Zenyaku Kogyo, Solasia J. Takizawa Honoraria: Chugai, Kyowa Kirin N. Fukuhara Honoraria: Chugai, Genmab, AbbVie, Takeda, Eli Lilly, AstraZeneca, Meiji Seika, Ono, Janssen, Bristol-Myers Squibb, Eisai, Kyowa Kirin, Symbio, Novartis Research funding: Chugai, Genmab, AbbVie, Takeda, Eli Lilly, Incyte, Chordia Therapeu D. Ennishi Honoraria: Eisai, Kyowa Kirin, Chugai Research funding: Nippon Shinyaku, Chugai Y. Minami Consultant or advisory role: Takeda, Novartis Honoraria: Bristol-Myers Squibb, Novartis, Pfizer, Daiichi Sankyo, Astellas Research funding: CMIC, Bristol-Myers Squibb, Novartis, Takeda, Chugai, Ono Y. Atsuta Consultant or advisory role: Meiji Seika, JCR Pharmaceuticals, Kyowa Kirin Honoraria: Novartis, AbbVie H. Kiyoi Honoraria: Novartis, Astellas, AbbVie, Chugai Research funding: Zenyaku Kogyo, Nippon Shinyaku, Chugai, Astellas, Kyowa Kirin, Takeda, Sumitomo Pharma, Sanofi, Eisai, Ono, FUJIFILM, Kyowa Kirin, Otsuka, Perseus Proteomics, Daiichi Sankyo, CURED, Bristol-Myers Squibb, AbbVie

17th International Conference on Malignant Lymphoma, Palazzo dei Congressi, Lugano, Switzerland, 13 - 17 June, 2023.

Introduction: In pts with newly diagnosed DLBCL, standard treatment with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) has a 5-year progression-free survival (PFS) rate of 67.0%, 58.4%, and 45.8% for International Prognostic Index (IPI) 2, 3, and 4–5, respectively (Ruppert et al., Blood 2020). Epcoritamab is a subcutaneously administered, bispecific antibody that binds CD3 on T cells and CD20 on B cells, inducing potent and selective T-cell–mediated killing of malignant CD20+ B cells (Hutchings et al., Lancet 2021). Epcoritamab monotherapy demonstrated deep and durable responses (overall response rate [ORR], 63%; complete response rate, 39%; median duration of response, 12 months) and was generally well tolerated in pts with relapsed/refractory (R/R) aggressive, large B-cell lymphoma (LBCL) (Thieblemont et al., J Clin Oncol 2022). Results from an ongoing phase 1/2 study in high-risk pts with newly diagnosed DLBCL (EPCORE NHL-2 arm 1; NCT04663347) show that epcoritamab + R-CHOP has promising efficacy and a manageable safety profile in high-risk pts with IPI 3–5. Among efficacy-evaluable pts (n = 31), ORR was 100% and complete metabolic response (CMR) was 77%; cytokine release syndrome (CRS) events (n = 17/33; 52%) were mostly low-grade, had predictable timing, and did not lead to treatment discontinuation (Falchi et al., ASCO 2022, abstract 7523). These encouraging data support further evaluation of epcoritamab + R-CHOP for the treatment of newly diagnosed DLBCL. Methods: This phase 3, global, multicenter, open-label study (NCT05578976) evaluates the efficacy and safety of epcoritamab + R-CHOP in adults newly diagnosed with one of the following CD20+ DLBCL (de novo or transformed from follicular lymphoma [FL]): 1) DLBCL, not otherwise specified (NOS); 2) high-grade B-cell lymphoma with MYC and BCL-2 and/or BCL-6 rearrangement; 3) T-cell/histiocyte–rich LBCL; 4) Epstein-Barr virus–positive DLBCL, NOS; or 5) FL grade 3b. Other key eligibility criteria include IPI ≥2 (pts with IPI 2 not to exceed ∼30% of total pts), ECOG PS 0–2, and ≥1 measurable disease site. Approximately 900 pts will be randomized 2:1 to either epcoritamab + R-CHOP (6 cycles, followed by 2 cycles of epcoritamab) or R-CHOP (6 cycles, followed by 2 cycles of rituximab). The primary efficacy endpoint is PFS in pts with IPI 3–5 (based on IRC assessment per Lugano criteria). The secondary efficacy endpoints are PFS in pts with IPI 2–5, event-free survival, CMR, overall survival, and minimal residual disease negativity. Safety endpoints include incidence and severity of treatment-emergent adverse events (AEs), serious AEs, and AEs of special interest (CRS, immune cell–associated neurotoxicity syndrome, and clinical tumor lysis syndrome). Enrollment began in January 2023 globally. © 2023 American Society of Clinical Oncology, Inc. Reused with permission. This abstract was accepted and previously presented at the 2023 ASCO Annual Meeting. All rights reserved. The research was funded by: This study was funded by AbbVie and Genmab. Keywords: aggressive B-cell non-Hodgkin lymphoma, combination therapies, immunotherapy Conflicts of interests pertinent to the abstract. L. H. Sehn Consultant or advisory role AbbVie, Amgen, AstraZeneca, BeiGene, BMS/Celgene, Genentech/Roche, Incyte, Janssen, Kite/Gilead, Merck, Seattle Genetics Research funding: Teva, Roche/Genentech M. Chamuleau Consultant or advisory role AbbVie, Novartis, Incyte Research funding: BMS, Gilead, GenMab G. Lenz Consultant or advisory role Roche, Gilead, Janssen, Bayer, BMS, Novartis, AbbVie, Incyte, Genmab, Karyopharm, Constellation, ADC Therapeutics, Sobi, Miltenyi, PentixaPharm, Genase, Immagene, Hexal, Lilly Research funding: Janssen, Bayer, MorphoSys, AstraZeneca Other remuneration: Invited Speaker: Roche, BMS, Novartis, AbbVie, Incyte, Sobi, Hexal M. R. Clausen Consultant or advisory role AbbVie, Genmab, Janssen and Kite/Gilead C. Haioun Consultant or advisory role AbbVie, Genentech/Roche, Incyte, Kite/Gilead, Miltenyi A. Davies Honoraria: Roche, Kite, Incyte, BMS, AstraZeneca, AbbVie, Genmab Research funding: Roche, AstraZeneca, MSD, Cellcentric Educational grants: Roche T. Oki Employment or leadership position: AbbVie E. Szafer-Glusman Employment or leadership position: AbbVie R. Conlon Employment or leadership position: AbbVie Stock ownership: AbbVie H. Chiou Employment or leadership position: AbbVie D. Ipe Employment or leadership position: AbbVie B. Elliot Employment or leadership position: Genmab Stock ownership: Genmab J. Wu Employment or leadership position: AbbVie G. Salles Consultant or advisory role AbbVie, Bayer, BeiGene, BMS/Celgene, Epizyme, Genentech/Roche, Genmab, Incyte, Janssen, Kite/Gilead, Loxo, Miltenyi, MorphoSys, Novartis, Rapt, Regeneron, Takeda

An unusual cause of adrenal insufficiency with elevation of 17-hydroxyprogesterone: case report

BackgroundWe present an intriguing case of primary adrenal lymphoma, with associated primary adrenal insufficiency (PAI), in a patient presenting a transitory partial 21-hydroxylase deficiency during the active phase of the adrenal disease.Case presentationAn 85-years old woman was referred because of worsening asthenia, lumbar pain, generalized myalgia and arthralgia. During investigations a computed tomography (CT) scan evidenced two large bilateral adrenal masses, highly suspicious for primary adrenal tumor. The hormonal assessment revealed very low levels of morning plasma cortisol and 24-h urinary cortisol, elevated ACTH levels with low plasma concentration of aldosterone, pointing to the diagnosis of PAI. After diagnosis of PAI our patient started glucocorticoid and mineralcorticoid replacement therapy with clinical benefit. In order to further characterize the adrenal lesions, adrenal biopsy, was performed. The histology revealed a high grade non-Hodgkin lymphoma with an immunophenotype consistent with intermediate aspects between diffuse large B-cell and Burkitt lymphoma, with a high proliferation index (KI-67 > 90%). The patient received chemotherapy with epirubicin, vincristine, cyclophosphamide, and rituximab, associated with methylprednisolone that resulted in a complete clinical and radiological remission within one year. After 2 years from the diagnosis and a total of 6 cycles of rituximab, the patient was in good clinical condition and was taking only the replacement therapy for PAI. The patient initially presented also a slight increase of 17-hydroxyprogesterone (17-OHP) for age that normalize after resolution of lymphoproliferative disease.ConclusionsIn the presence of bilateral adrenal disease and/or in the presence of signs and symptoms of PAI clinicians must exclude the presence of PAL. The evidence of elevated ACTH-stimulated 17-OHP levels also in patients with other adrenal masses, together with the detection of elevated basal 17-OHP levels in our patient make it more plausible, in our view, an effect of the lesion on the “healthy” adrenal tissue residue than a direct secretory activity by the adrenal tumor.

Waldenström macroglobulinemia with secondary pure red cell aplasia in a patient with metastatic castrate resistant prostate cancer receiving an immune checkpoint inhibitor: a case report

BackgroundHypoproliferative anemia is a frequently encountered adverse event in cancer patients receiving immune checkpoint inhibitors (ICI). Secondary pure red cell aplasia (PRCA) is a rare but recognized immune related adverse event. With the burgeoning use of ICIs, the association of secondary PRCA with an underlying lymphoproliferative disorder is often overlooked.Case presentationWe report a case of a 67-year-old non-Hispanic Caucasian male with metastatic castrate resistant prostate cancer, who developed severe transfusion dependent anemia with reticulocytopenia while receiving treatment with olaparib and pembrolizumab. His bone marrow findings demonstrated erythroid hypoplasia, in addition to a CD5-negative, CD10-negative monotypic B-cell population and a somatic MYD88L265P mutation. With a presence of an IgM-paraprotein, he was diagnosed with Waldenström macroglobulinemia (WM) with secondary PRCA and treated with 6 cycles of bendamustine and rituximab. He achieved a complete response with this regimen and was transfusion independent.ConclusionIn this case, underlying WM was uncovered through systematic investigation of anemia caused by ICI therapy. This report highlights the possibility of a lymphoproliferative disorder in patients with concerns for PRCA with prior ICI exposure. If identified, treating the underlying lymphoproliferative disorder is highly efficacious in the management of the secondary PRCA.

Off-label use of rituximab in patients with systemic lupus erythematosus with extrarenal disease activity: a retrospective study and literature review.

Off-label rituximab is commonly used for patients with systemic lupus erythematosus (SLE) with extrarenal disease activity. The outcomes and tolerability of rituximab in adult patients with non-renal SLE treated at our hospital from 2013 to 2020 were described. Patients were followed-up until December 2021. Data were retrieved from electronic medical records. Response was classified into complete, partial or no response according to the Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI 2 K)-based definitions. A total of 44 cycles were administered to 33 patients. Median age was 45 years and 97% were female. Median follow-up was 5.9 years (IQR 3.7-7.2). The most frequent symptoms that motivated rituximab use were thrombocytopenia (30.3%), arthritis (30.3%), neurological manifestations (24.2%) and cutaneous lupus (15.2%). After most treatment cycles a partial remission was achieved. The median SLEDAI-2 K score declined from 9 (IQR 5-13) to 1.5 (IQR 0-4) (p < 0.00001). The median number of flares significantly declined after receiving rituximab. Platelet counts significantly improved in patients with thrombocytopenia and patients with skin disorders or neurological manifestations also had a partial or complete response. Only 50% of patients with a predominant joint involvement had either a complete or a partial response. The median time to relapse after the first cycle was 1.6 years (95% CI, 0.6-3.1). Anti-dsDNA levels decreased significantly after rituximab from a median of 64.3 (IQR 12-373.9) to 32.7 (IQR 10-173), p = 0.00338. The most frequent adverse events were infusion-related reactions (18.2%) and infections (57.6%). All patients needed further treatment to maintain remission or to treat new flares. A partial or complete response was documented after most rituximab cycles in patients with non-renal SLE. Patients with thrombocytopenia, neurolupus, and cutaneous lupus had better response than those with a predominant joint involvement.

Sustained cell-mediated but not humoral responses in rituximab-treated rheumatic patients after vaccination against SARS-CoV-2.

B-cell depleting monoclonal antibodies are associated with increased COVID-19 severity and impaired immune response to vaccination. We aimed to assess the humoral and cell mediated (CMI) immune response after SARS-CoV-2 vaccination in rituximab (RTX)-treated rheumatic patients. Serum and whole blood samples were collected from RTX-treated rheumatic patients 3-6 months after last vaccination against SARS-CoV-2. Serum was tested by ELISA for quantitative detection of anti-spike SARS-CoV-2 IgG. Cell-mediated variant-specific SARS-CoV-2 immunity (CMI) was assessed by interferon-γ release assay Covi-FERON FIA. Patients were interviewed for breakthrough COVID-19 infection (BTI) 3 months post sampling. Sixty patients were studied after a median (IQR) of 179 (117-221.5) days from last vaccine to sampling. Forty (66.7%) patients had positive Covi-FERON and 23 (38.3%) had detectable anti-spike IgG. Covi-FERON positive patients had lower median RTX cumulative dose [6 (4-10.75) vs 11 (6.75-14.75) grams, (P = 0.019)]. Patients with positive anti-spike IgG had received fewer RTX cycles [2 (2-4) vs 6 (4-8), P = 0.002] and cumulative dose [4 (3-7) vs 10 (6.25-13) grams, P = 0.002] and had shorter time from last vaccination to sampling [140 (76-199) vs 192 (128-230) days, P = 0.047]. Thirty-seven percent were positive only for Covi-FERON and 7% only for anti-spike IgG. Twenty (33.3%) BTI occurred post sampling, exclusively during Omicron variant predominance. The proportion of patients with CMI response against Delta variant was lower in patients who experienced BTI (25% vs 55%, P = 0.03). Four out of ten RTX-treated vaccinated patients show lasting cell-mediated immune response despite undetectable anti-spike antibodies. Cumulative RTX dose affects both humoral and cell-mediated responses to SARS-CoV-2 vaccines. Cell-mediated immune responses call for attention as a vaccine efficacy marker against SARS-CoV-2.

Anti-GABA-A Receptor Antibody-Mediated Epilepsia Partialis Continua After Treatment With Alemtuzumab: A Case Report.

Patients with anti-GABA-A receptor encephalitis characteristically experience therapy-refractory epileptic seizures. General anesthesia is often required to terminate refractory status epilepticus. The immunologic mechanisms leading to antibody formation remain to be elucidated. Described triggers of anti-GABA-A autoimmunity are tumors, mainly thymomas, and herpes simplex encephalitis. We present a young woman with prediagnosis of relapse remitting multiple sclerosis (MS), treated with interferons, natalizumab, and alemtuzumab. Six months after one and only cycle of alemtuzumab, speech arrest and behavioral changes with aggressive and anxious traits appeared. She showed increasing motor convulsions resulting in focal status epilepticus. Anti-GABA-A receptor antibodies in CSF and serum were confirmed in different external laboratories, in a more extensive analysis after antibodies against NMDAR, CASPR2, LGI1, GABABR, and AMPAR were ruled out during in-house examination. Clinical condition improved temporarily with cortisone therapy, plasmapheresis, and IVIG but deteriorated rapidly after steroid discontinuation, resulting in brain biopsy. On histopathologic confirmation consistent with anti-GABA-A receptor antibody-associated CNS inflammation, completing the first rituximab cycle, continuing oral corticosteroids and supplementing immunosuppression with cyclosporine A led to quick recovery. Our case describes a severe autoantibody-induced encephalitis in a young patient with MS, with alemtuzumab as a potential trigger for anti-GABA-A receptor encephalitis.

The Importance of Patient-Focused Drug Development in Pemphigus and Pemphigoid

The Importance of Patient-Focused Drug Development in Pemphigus and Pemphigoid

Primary EBV Lymphoproliferative Disease Responsive to Therapy in a Patient with CTLA4-Haploinsufficiency

Epstein-Barr virus lymphoproliferative disease (EBV-LPD) occurs most often in patients with acquired immunosuppression. However, several inborn errors of immunity have been associated with primary EBV-LPD, including pathogenic variants in SH2D1A, ITK, MAGT1, CORO1A, CD27, CTPS1, RASGRP1, and ZAP70 (PMID29942301,34239742). Here, we present a patient with primary EBV-LPD in the setting of CTLA-4 haploinsufficiency. JC is a 25yo male with Evans syndrome, hypogammaglobulinemia, and central nervous system vasculitis who presented to the NIH for evaluation of EBV-LPD. After a complicated course of legionella pneumonia at age 23, he developed recurrent fevers, respiratory distress, hypoxia, and night sweats responsive to dexamethasone. Chest CT revealed innumerable bilateral pulmonary nodules and masses with mediastinal hilar lymphadenopathy and scattered ground glass opacities. Transbronchial biopsy demonstrated EBV-positive B-cell LPD with extensive necrosis and clonal gene rearrangements. He responded well to 1 cycle of rituximab. Two years later, he again had fever, dyspnea on exertion, and hypoxia requiring glucocorticoids. Chest CT revealed ground glass opacities of the lungs, lung nodules/masses, and consolidation. Lung biopsy showed T and B-cell infiltrates, EBV+ B-cells by immunohistochemistry, and a clonal B-cell population (Figure 1). His course was also complicated by concurrent Pneumocystis Jirovecii (PJP) infection. He received 1 cycle of rituximab, trimethoprim-sulfamethoxazole, and sirolimus for treatment of his EBV-LPD, PJP, and underlying CTLA-4 haploinsufficiency respectively with symptomatic and radiologic response (Figure 2). [Display omitted] [Display omitted] NIAID whole exome sequencing (WES) revealed 2 compound heterozygous variants in CTLA-4 in trans: a novel pathogenic variant c.373G > A, p.Gly125Arg, and a non-pathogenic c.326G > A, p.Gly109Glu, shared with his mother(allele frequency of 0.000367 popmaxv.3.1.1 and Cadd score 17). Other variants that may contribute to EBV-LPD are under investigation.EBV-LPD in CTLA-4 haploinsufficiency is rare, previously reported in only 2 pediatric cases (PMID34329649). Additionally, WES revealed compound heterozygous variants in CTLA-4; however, only 1 variant was proven pathogenic. While this patient initially demonstrated excellent response to first line therapy, long-term prognosis is guarded. Abatacept was not included in this patient’s treatment because of an association with progressive LPD in patients with and without CTLA-4 haploinsufficiency. Immune reconstitution with bone marrow transplantation will likely be required for permanent disease control.

A Case of CNS Lymphoma Imitating Post-Vaccination ADEM (P14-13.003)

<h3>Objective:</h3> NA <h3>Background:</h3> A previously healthy 42-year-old male presented acutely with slurred speech, confusion and urinary incontinence several weeks after receiving a COVID booster and Tdap vaccination. <h3>Design/Methods:</h3> NA <h3>Results:</h3> Initial workup revealed multifocal enhancing T2 white matter hyperintensities in the bilateral frontal/parietal lobes, corpus callosum and bilateral midbrain, sparing the cerebellum and spinal cord. Contrast enhanced CT of the chest, abdomen and pelvis showed no masses or lymphadenopathy. Cerebrospinal fluid analysis showed a mild lymphocytic pleocytosis (12) with normal RBC, protein, glucose, negative meningitis/encephalitis PCR, cytology and autoimmune encephalitis antibodies. Serum testing was negative for HIV, RPR, NMO, MOG and antinuclear antibodies. Working diagnosis of acute disseminated encephalomyelitis was made and he was started on IV methylprednisolone 1g daily for 5 days followed by an oral steroid taper with a weekslong improvement in symptoms to his neurologic baseline followed by relapse. We repeated MRI brain which demonstrated mixed response to treatment and two repeat CSF analyses showed 2 WBC with negative cytology. Given symptom recurrence, 1g daily IV methylprednisolone was re-administered for 5 days with another brief improvement, followed by IVIG 2g/kg over 5 days. Despite aggressive immunotherapy, his symptoms continued to worsen, and he was referred for brain biopsy confirming the diagnosis of primary diffuse large B-cell lymphoma of the CNS. At the direction of neuro-oncology, the patient underwent 6 cycles of systemic high-dose methotrexate and rituximab and 2 cycles of temozolomide with PET/MRI evidence of complete response (no lesion enhancement). His performance status improved significantly, and he underwent autologous hematopoietic stem cell transplant for consolidative therapy. <h3>Conclusions:</h3> CNS lymphoma should be considered in the differential for contrast-enhancing FLAIR hyperintensities and can be steroid responsive. Brain biopsy should not be delayed in cases where CNS lymphoma is a leading differential as it can guide early disease management and help improve patient outcomes. <b>Disclosure:</b> Dr. Frank has nothing to disclose. Dr. Alalami has nothing to disclose. An immediate family member of Dr. Livingston has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Sanofi. An immediate family member of Dr. Livingston has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Sanofi. The institution of an immediate family member of Dr. Livingston has received research support from Vertex. The institution of an immediate family member of Dr. Livingston has received research support from Roche. The institution of an immediate family member of Dr. Livingston has received research support from AstraZeneca. The institution of an immediate family member of Dr. Livingston has received research support from Enanta. Dr. Hu has nothing to disclose. Dr. Shadbehr has nothing to disclose.

Retrospective analysis of the long-term therapeutic effectiveness and safety profile of rituximab in the treatment of mucous membrane pemphigoid in a German university center between 2008 and 2019.

The B-cell-depleting anti-CD20 antibody rituximab (RTX) is often used as an adjuvant drug for the treatment of refractory cases of mucous membrane pemphigoid (MMP). This study aims to determine the therapeutic effectiveness and the safety profile of RTX in MMP. The medical records of all cases of MMP treated with RTX between 2008 and 2019 in our university medical center located in northern Germany, which specialized in autoimmune blistering skin diseases, were retrieved and systemically analyzed for treatment responses and potential adverse events over a median period of 27 months. We identified 18 MMP patients who received at least one cycle of RTX to treat MMP. RTX was always used as an adjuvant treatment, and its application did not change concomitant treatments. Under treatment with RTX, 67% of the patients achieved an improvement in their disease activity within 6 months. This was also reflected in a statistically significant reduction in the Mucous Membrane Pemphigoid Disease Index (MMPDAI) activity score. The frequency of infections under RTX treatment increased only slightly. The use of RTX is associated with an attenuation of MMP in a large proportion of MMP patients in our study. At the same time, its application was not found to further increase the susceptibility of the most strongly immunocompromised population of MMP patients to opportunistic infections. Collectively, our results suggest that the potential benefits of RTX outweigh its risks in patients with refractory MMP.