Primary cardiac lymphoma: an analysis of presentation, treatment, and outcome patterns

BACKGROUND:

Primary cardiac lymphoma (PCL) represents a rare subset of non‐Hodgkin lymphoma, characterized by poor outcomes. The authors aimed to construct a framework of known clinical presentations, diagnostic features, disease complications, treatment, and outcomes to improve prognostication.

METHODS:

Individual patient data were obtained from defined cases of PCL (1949‐2009) and systematically analyzed.

RESULTS:

The authors report results of a review of 197 cases of PCL, with half of all cases reported since 1995. Survival was affected by 4 factors: immune status, left ventricular involvement, presence of extra‐cardiac disease, and arrhythmia. Median overall survival (OS) for immunocompromised and immunocompetent was 3.5 months (m) and not reached, respectively (HR 0.29, 95% CI, 0.13‐0.68; P = .004). LV involvement was uncommon (26%) and associated with an OS of only 1m, whereas patients free of LV involvement had a median OS of 22m (HR 0.28, 95% CI, 0.12‐0.64; P = .002). Patients with extracardiac disease had shorter median OS compared with those without (6m vs 22m, HR 0.49, 95% CI, 0.26‐0.91; P = .02). Those patients with an arrhythmia of any type had a median OS that was not reached (n = 55), whereas those without rhythm disturbances (n = 41) had median OS of 6m (HR 0.51, 95% CI, 0.29‐0.91; P = .024). Overall response rate to therapy was 84%, with long‐term OS over 40%.

CONCLUSIONS:

The current study presents the largest analysis of PCL to date. The data demonstrate that PCL is now more frequently diagnosed premortem and appears to have reasonable response rates. Lack of LV involvement and the presence of arrhythmias are associated with improved survival. Cancer 2011. © 2010 American Cancer Society.     

重视转化型淋巴瘤的生物学特点及诊治策略

 1、2级滤泡性淋巴瘤转化为弥漫大细胞型淋巴瘤（DLCL）或波基特样淋巴瘤即视为转化型淋巴瘤（TL）。TL常表现为生发中心来源,主要免疫表型与滤泡性淋巴瘤（FL）相同,如CD+10／BCL-6+。PET-CT 显示SUV值较高的部位活检取病理,可提高转化型淋巴瘤的确诊率。初次诊断后10年TL的发生率约30 %。TL患者的预后欠佳,中位生存期仅为1～2年。大剂量化疗联合自体干细胞移植（HDCT-ASCT）、异基因造血干细胞移植、放射免疫疗法及苯达莫斯汀对TL均有一定的疗效。     

Heterogeneity of response and survival in diffuse histiocytic lymphoma after BACOP therapy (bleomycin, doxorubicin, cyclophosphamide, vincristine, prednisone)

Diffuse 'histiocytic' lymphoma (DHL) is heterogeneous pathologically, consisting of four subtypes within Lukes-Collins; large-cleaved (LC), large non-cleaved (LNC), immunoblastic sarcoma of B cells (B-IBS), and immunoblastic sarcoma of T-cells (T-IBS). This heterogeneity is also recognized in the Cooperative Working Formulation on non-Hodgkin's lymphoma. Prior studies have suggested clinical heterogeneity of DHL as well, although conclusions were hampered by small numbers, and lack of therapeutic uniformity. We treated 57 patients with advanced DHL, using BACOP: 22 LNC, 16 T-IBS, 13 B-IBS, six LC. Complete remission rate for LNC was 64 per cent (14/22); B-IBS was 54 per cent (7/13); LC was 33 per cent (2/6); T-IBS was 25 per cent (4/16). (p = 0.10). Median survival for LNC was 27.8 months, B-IBS was 25.9, LC was 14, T-IBS was 12.0. The survival was significantly shorter for T-IBS patients when compared to the others (p = 0.01). By multi-variate analysis, histologic subtype (p = 0.02), age (p = 0.03), and stage (p = 0.06) were significant and independent prognostic variables in predicting survival. We conclude that LNC may respond the most favourably to BACOP, whereas alternative regimens appear necessary for patients with T-IBS.     

Primary pancreatic lymphoma: a case report, literature review, and proposal for nomenclature

Primary neoplasms of the pancreas are most often adenocarcinoma. Non-Hodgkin's lymphoma (NHL) involving the pancreas is less common but well documented; the pancreas as the primary site of NHL is rare. The majority of patients with pancreatic cancer, whether it is adenocarcinoma or lymphoma, present with a mass in the head of the gland. Pancreatic lymphoma is often described as a large homogeneous mass with extra-pancreatic extension, with or without associated lymphadenopathy. Less common presentations are masses in the body or tail, or more rarely diffuse involvement of the pancreas. We present a case of diffuse pancreatic lymphoma with extra-pancreatic dissemination to the spleen and lymph nodes, and review the literature on pancreatic lymphoma. Because the definition of pancreatic lymphoma and primary pancreatic lymphoma varies, we also propose a nomenclature system to make future studies of pancreatic lymphoma more comparable.     

Phenotyping of canine lymphoma with monoclonal antibodies directed at cell surface antigens: Classification,morphology, clinical presentation and response to chemotherapy

Forty cases of naturally occurring canine lymphoma were studied using a panel of murine monoclonal antibodies which identify defined subsets of normal canine lymphocytes. The distribution of phenotypes was similar to that which is seen in man in that the majority (78 per cent) of canine lymphomas were of B-cell origin but a definite minority were phenotypically of T-cell (10 per cent) or non-B, non-T-cell (12 per cent) origin. The expression of Ia-like antigens was restricted to B-cell neoplasms. Within each histologic subgroup of canine lymphomas there was considerable heterogeneity of cell surface marker expression. Immunophenotype appeared to correlate with clinical presentation. Finally, the reactivity of lymphoma cells with murine monoclonal antibody DLy-6, an antibody which appears to react with a differentiation antigen on canine B and T cells, strongly predicted the outcome of initial induction chemotherapy in that all ten evaluable dogs with DLy-6^? tumors achieved complete responses to initial chemotherapy while only four of 11 dogs with DLy-6⁺ tumors responded completely.     

Primary gastrointestinal lymphomas: A radiological–pathological review. Part 1: Stomach,oesophagus and colon

Primary gastrointestinal lymphomas are most common in the stomach, followed by small intestine and then colon. The most frequently used pathology classification of lymphomas is the Revised European and American Lymphoma /World Health Organization classification. The correlation of radiological morphology with histology is relatively poor, although characteristic subtypes will be discussed. In the stomach, the majority of primary lymphomas are of B‐cell origin of mucosa‐associated lymphoid tissue (MALT) type. Low‐grade MALT lymphomas are associated with Helicobacter pylori infection and often respond to eradication of this organism. Radiological features include thickened folds, nodularity, depressed lesions, ulcers, prominent areae gastricae. High‐grade (large B‐cell) tumour patterns include infiltrative, polypoid, nodular, ulcerated or a combination. Endoscopy, endoscopic ultrasound and CT are important in diagnosis and staging, although appearances on barium studies should be recognized. Primary colonic lymphomas are rare. Most are of B‐cell origin. Focal and diffuse forms are seen, the former producing polypoid or nodular or cavitating masses and the latter producing ulcerative or nodular (polyposis) patterns on imaging. Even when circumferential, lymphoma rarely causes obstruction. Small bowel lymphomas will be discussed in the forthcoming part 2 of this review.     

Peripheral T-Cell Lymphomas Respond Well to Vincristine, Adriamycin, Cyclophosphamide, Prednisone and Etoposide (VACPE) and Have a Similar Outcome as High-Grade B-Cell Lymphomas

Peripheral T-cell lymphomas (PTCL) represent a heterogeneous group of T-cell malignancies including subentities with favourable (large cell anaplastic) or unfavourable (pleomorphic) prognosis. The clinical outcome of PTCL has been controversially discussed, but a worse prognosis than high-grade B-cell Non-Hodgkin's lymphomas (NHL) has been postulated by most authors. In this report we summarize the results of a prospective comparative study investigating the therapy outcome of 27 patients (pts) with PTCL and 55 pts. with high grade B-cell NHL and give an overview of therapy studies in PTCL. The histological sub-types were 14 pleomorphic, 8 large-cell anaplastic (Ki-1+), 2 angioimmunoblastic (AILD) and 3 other PTCL. In three patients the PTCL was associated with non-tropical sprue (11%). Nineteen patients presented with an advanced stage of disease (stage III and IV, 70%), 17 (63%) pts. had B-symptoms. The patients were treated with vincristine 2 mg dl, adriamycin 25 mg/m² dl-3, cyclophosphamide 800 mg/m² dl, prednisone 60 mglm² dl-7 and etoposide 120 mg/m² dl-3 (VACPE). In 77% of pts. with PTCL and 84% of patients with high-grade B-cell NHL a complete remission (CR) was achieved. 75% of the complete responders with PTCL and 70% with B-NHL are still in ongoing CR. The subgroup of large-cell anaplastic attained a CR in 88%. The median observation time is 44 months (1+-77+). The probability of 1-, 3- and 5-year overall and disease-free survival for the T-cell group were 76%, 54%, 48% and 76%, 62%, 62%, respectively according to Kaplan-Meier. There was no significant difference regarding the remission rate, the overall-, event-free or disease-free survival compared to high-grade B-cell lymphomas.

In conclusion, the VACPE regimen is an effective and feasible regimen in the management of PTCL achieving complete remissions in a large proportion of patients.     

Prognostic value of MYC rearrangement in cases of B-cell lymphoma, unclassifiable, with features intermediate between diffuse large B-cell lymphoma and Burkitt lymphoma

BACKGROUND:

B‐cell lymphoma, Unclassifiable with features intermediate between diffuse large B‐cell lymphoma (DLBCL) and Burkitt lymphoma, for convenience referred to here as unclassifiable B‐cell lymphoma, is a category in the 2008 World Health Organization system used for a group of histologically aggressive neoplasms that are difficult to classify definitively. Currently, there is no established standard therapy for these neoplasms.

METHODS:

The authors assessed MYC status and correlated it with treatment response and outcome in a group of 52 patients with unclassifiable B‐cell lymphoma treated with either a standard DLBCL regimen (R‐CHOP [rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisolone‐related therapy]) or more intensive regimens, such as R‐hyper‐CVAD (rituximab plus hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone alternating with high‐dose methotrexate and cytarabine). The regimens were selected by the treating clinicians based on the overall clinical and pathological findings.

RESULTS:

Thirty (58%) unclassifiable B‐cell lymphomas had MYC abnormalities (MYC⁺) including 27 with rearrangement, 2 with amplification, and 1 with both. The MYC⁺ and MYC^? groups were similar in their age distribution and International Prognostic Index scores. Progression‐free survival of patients with MYC⁺ unclassifiable B‐cell lymphoma treated initially with R‐CHOP was significantly worse than patients treated with R‐hyper‐CVAD (P = .0358). In contrast, for the MYC^? unclassifiable B‐cell lymphoma group, some patients responded to R‐CHOP, and others were refractory to R‐hyper‐CVAD.

CONCLUSIONS:

MYC aberrations are common in unclassifiable B‐cell lymphoma. The presence of MYC aberrations identifies a patient subset that requires more aggressive therapy than R‐CHOP. In contrast, MYC^? unclassifiable B‐cell lymphoma patients responded variably to either R‐CHOP or aggressive therapy, and the latter showed no survival advantage. Cancer 2011;. © 2011 American Cancer Society.     

Leukemic High Grade B Cell Lymphoma is Associated With MYC Translocation,Double Hit/Triple Hit Status,Transformation, and CNS Disease Risk: The Mayo Clinic Experience

Introduction: Leukemic involvement in high grade B cell lymphoma (L-HGBL) is rare and has been sparsely described in the literature. We report our experience in a large single institution multicenter academic setting. Materials and Methods: Medical records of patients with HGBL who received care at Mayo Clinic between 2003 and 2020 were reviewed. L-HGBL was confirmed by peripheral blood smear and flow cytometry with corroboration from tissue and bone marrow biopsy findings. Results: Twenty patients met inclusion criteria. All patients had significant bone marrow involvement by HGBL. Leukemic involvement presented in 11 of 20 (55%) in the de novo and 9 of 20 (45%) in the relapsed setting. Seven of 20 patients had DLBCL, NOS, 6 of 20 had transformation (t-DLBCL), 3 of 20 had transformed double/triple hit lymphoma (t-DHL/THL), 2 of 20 had double hit lymphoma (DHL), and 2 of 20 had HGBL with intermediate features between DLBCL and Burkitt lymphoma. Nine of 15 patients had MYC translocation. Based on Hans criteria, 11 of 20 had germinal center B-cell (GCB) cell of origin (COO) and 9/20 had non-GCB COO. Five of 11 de novo patients experienced CNS relapse/progression. All de novo patients received anthracycline-based chemoimmunotherapy. Eighteen of 20 patients died of progressive disease. Median overall survival was significantly better in the de novo compared to relapsed group (8.9 months vs. 2.8 months, P = .01). COO, MYC status, DHL/THL status, HGBL subtype, or treatment group did not demonstrate a significant effect on overall survival. Conclusion: L-HGBL carries a poor prognosis and is associated with MYC translocation, DHL/THL status, transformation, and high CNS risk. Novel therapeutic approaches are needed for L-HGBL.     

Efficacy and safety of clofarabine in relapsed and/or refractory non-Hodgkin lymphoma, including rituximab-refractory patients

BACKGROUND:

Currently, no standard therapy exists for patients with relapsed and/or refractory non‐Hodgkin lymphoma (NHL) who are ineligible for transplantation or who have failed after bone marrow transplantation. The authors of this report investigated the safety and efficacy of clofarabine (CLO) in these patients.

METHODS:

In a 2‐step, open‐label study, CLO (as a 1‐hour intravenous infusion given daily for 5 days) was given every 28 days (maximum, 6 cycles). In the phase 1 portion (n = 7; standard 3 + 3 study design), the dose was escalated by 2 mg/m² to determine the maximum tolerated dose (MTD). The phase 2 study (n = 26) was initiated at the MTD, and patients were followed until disease progression.

RESULTS:

Of 33 patients who were enrolled, 31 patients (median age, 69 years) were evaluable; 24% failed after previous stem cell transplantation, and 72% were rituximab‐refractory. The MTD for CLO was 4 mg/m². The overall response rate was 42%. Seven patients (23%) achieved a complete response, and 6 patients (19%) achieved a partial response. The median response duration was 5 months. Among the rituximab‐refractory patients, the overall response rate was 47% (complete response rate, 28%), and the median response duration was 7 months. At a median follow‐up of 14 months, 45% of patients remained alive (median overall survival, 10 months). Toxicity was mainly hematologic (≥60% of patients had neutropenia or thrombocytopenia). Nonhematologic toxicity included tumor lysis syndrome, infection, and renal insufficiency (in 6% of patients each). No treatment‐related mortality was observed.

CONCLUSIONS:

Single‐agent CLO was active and was tolerated well in patients with refractory NHL, including patients in a rituximab‐refractory subset. Reversible myelosuppression was the major toxicity. Study is registered at www.clinicaltrials.gov (NCT00156013). Cancer 2011. © 2010 American Cancer Society.     

Burkitt Lymphoma — Subtypes,Pathogenesis, and Treatment Strategies

Burkitt's lymphoma (BL) is a rare and highly aggressive Non-Hodgkin lymphoma (NHL) with a germinal center phenotype, a nearly universal myc oncogene translocation to an enhancer element and a proliferation index greater than 95%.¹ Bcl-2 is not expressed as opposed to double-hit or triple-hit lymphoma. Genetic mutations and aberrancy involving the phosphatidylcholine 3-kinase and cyclin-dependent kinase pathways are also involved.2, 3, 4, 5 Rarely patients present with stage I disease and others are considered as high risk if greater than stage I or with elevated LDH or masses greater than 10 cm.     

Fludarabine, cyclophosphamide, and dexamethasone (FluCyD) combination is effective in pretreated low-grade non-Hodgkin's lymphoma

Purpose: Fludarabine phosphate is effective as a single agent in low-grade non-Hodgkin's lymphoma (NHL). Combined with other antineoplastic agents it enhances the antitumor effect. Our aim was to define the therapeutic efficacy and toxicity of a combination of fludarabine, cyclophosphamide and dexamethasone (FluCyD) in patients with advanced low-grade lymphoma.Patients and methods: Twenty-five adults with pretreated advanced-stage low-grade NHL were treated with three-day courses of fludarabine 25 mg/m2/day, cyclophosphamide 350 mg/m2/day, and dexamethasone 20 mg/day, every four weeks for a maximum of six courses.Results: Of the 25 patients, 18 (72%) responded, 8 (32%) achieving CR and 10 (40%) PR. Seven were failures. The median follow-up was 21 months (5–26). Eight CR patients remain in CR after 5–21 months. Of 10 PR patients, 3 are in continuous PR without further treatment after 12, 17 and 18 months. Myelosuppression was the most prevalent toxic effect. Although severe granulocytopenia (granulocyte count nadir <500/µl) and thrombocytopenia (platelet count nadir <50,000/µl) occurred in only 10% and 16% of courses, respectively, slow granulocyte or platelet count recovery caused delay of 40% of the courses. Nine patients (36%) required discontinuation of therapy because of persistent granulocytopenia and/or thrombocytopenia: three after one course, three after 2–4 courses, and three after five courses. Thirteen infectious episodes in 11 patients complicated 11% of courses. Two of 10 patients monitored for the circulating EBV load showed increased viral load. One of these developed aggressive lymphoma. CD4+ lymphocytes declined from a pre-therapy median value of 425/µl to 141/µl post-treatment (P = 0.001). Non-hematologic toxicities were rare and mild.Conclusions: The combination of fludarabine with cyclophosphamide and dexamethasone is effective in pretreated advanced-stage low-grade NHL. It may broaden the range of therapeutic options in the salvage treatment of these patients. The main toxicity of this combination is prolonged myelosuppression that may cause treatment delay or withdrawal. The benefit of adding granulocyte colony-stimulating factor, particularly in patients with poor marrow reserve, needs to be investigated.     

我国血管内大B细胞淋巴瘤的临床亚型、诊治及预后分析

目的探讨我国血管内大B细胞淋巴瘤(intravascular large B-cell lymphoma,IVLBCL)不同亚型间临床表现、诊治及预后差异。方法系统检索并回顾性分析我国1994—2021年文献报道的185例IVLBCL。结果185例IVLBCL患者中共活检确诊178例,其中61.8%(81/131)有2个或2个以上器官受累。首发症状与辅助检查结果高度异质性。中枢神经系统(CNS)受累型35例,噬血细胞综合征相关型(HPS)29例,其他78例,未知43例。相比HPS型,CNS受累型不明原因发热发生率(25.7%vs 86.2%,P<0.001),贫血/血小板减少发生率(50.0%vs 100.0%,P=0.004),骨髓侵犯发生率(21.4%vs93.1%,P<0.001)以及接受化疗比例(40.0%vs 84.0%,P=0.001)较低。CNS受累型预后差于HPS相关型(2.0个月vs未到达,P<0.001)及其他型(2.0个月vs 23.0个月,P<0.001)。化疗组较非化疗组1年生存率升高(53.4%vs 2.7%,P<0.001)。结论我国IVLBCL临床表现具有高度异质性,CNS受累型预后较HPS相关型差,化疗可显著改善预后。     

Phase II study of infusional chemotherapy with doxorubicin, vincristine and etoposide plus cyclophosphamide and prednisone (I-CHOPE) in resistant diffuse aggressive non-Hodgkin's lymphoma: CALGB 9255

Background:Patients with resistant diffuse aggressivenon-Hodgkin's lymphoma (DA-NHL) have a poor prognosis. Studies have suggestedinfusional therapy may be beneficial. Patients and methods:This trial used an infusional regimen calledI-CHOPE in resistant patients who had previously received only bolus CHOPE orCHOP regimen. Resistance was defined as: a) primary refractory disease, b)progression on therapy, c) partial response, d) complete remission lastingless than one year. Eligibility criteria included a diagnosis of DA-NHL (IWFE-H), no prior irradiation and adequate organ function. Results:Thirty-seven patients were entered and twenty-nine wereeligible. Reasons for ineligibility were incorrect histology (5) and other(3). The median age was 57 years (range 29–81) with 21 males. Theperformance status scores were: 0 (12 patients); 1 (9 patients); 2 (8patients). Prior therapy consisted of standard CHOP (26 patients), bolus CHOPE(2 patients), high dose CHOP (1 patient). Therapy consisted of a 120 hourcontinuous intravenous infusion of doxorubicin 10 mg/m²/day,vincristine 0.28 mg/m²/day (maximum 0.4 mg/day), and etoposide 48mg/m²/day. Cyclophosphamide 750 mg/m² was given as aniv bolus day 6 and prednisone was given at 100 mg/day p.o. on days 1–5.G-CSF was allowed for myelosuppression. The overall response rate was48% (CR 17%; PR 31%). Freedom from progression was24% at six months and 8% at one year. Survival was 69%at six months and 40% at one year. In an exploratory analysis a priorCR or PR predicted response to I-CHOPE. Twelve of sixteen patients who had aCR/PR on previous therapy responded while two of thirteen who had no priorresponse, responded to I-CHOPE (P= 0.003). The toxicity wastolerable with grade 3–4 hematologic toxicity being leucopenia94% and thrombocytopenia 41%. The grade 3–4non-hematologic toxicities were infection in 28%, phlebitis in11%, and stomatitis in 15%. Conclusions:I-CHOPE can induce responses in this group ofpatients with a poor prognosis, but most were seen in those who had previouslyhad a response to bolus chemotherapy.     

弥漫大B细胞淋巴瘤myc、bcl-2和bcl-6蛋白表达与基因异常的相关性研究

目的 探讨多重基因异常在弥漫大B细胞淋巴瘤(DLBCL)中的发生情况及其与蛋白高表达之间的关系.方法 收集2012年1月至2016年12月确诊的DLBCL非特指型患者50例,采用免疫组织化学法检测c-myc、bcl-2及bcl-6蛋白表达情况,采用间期荧光原位杂交(I-FISH)方法检测3个基因异常情况.结果 50例DLBCL患者中,男性27例,女性23例;年龄3~85岁,中位年龄50岁.发病部位:淋巴结23例(46.00%),结外27例(54.00%),以胃肠道最为多见(13例,48.15%).免疫组织化学检测c-myc蛋白阳性率94.00%(47/50),阳性细胞超过40%者41例(82.00%);bcl-2蛋白阳性率84.00%(42/50),阳性细胞超过70%者38例(76.00%);18例(36.00%)同时高表达c-myc和bcl-2.FISH检测结果显示,7例(14.00%)c-myc断裂,2例(4.00%)扩增;6例(12.00%)bcl-2断裂,4例(8.00%)扩增;8例(16.00%)bcl-6断裂,3例(6.00%)扩增,1例(2.00%)同时断裂及扩增;4例(8.00%)检测到多重基因异常,其中1例(2.00%)c-myc合并bcl-2基因异常,2例(4.00%)c-myc合并bcl-6基因异常,为双重打击淋巴瘤(DHL),1例(2.00%)同时检测到c-myc、bcl-2及bcl-6基因异常,为三重打击淋巴瘤(THL).4例多重基因异常病例中,3例起源于生发中心B细胞(GCB),1例起源于非GCB.18例c-myc和bcl-2蛋白双高表达组仅有3例(16.67%)检测到多重基因异常,包括2例DHL和1例THL.结论 多重基因异常在DLBCL中的检出率为8.00%.基因异常与蛋白高表达之间无明显相关性,DHL的检出依赖于分子遗传学检测.     

A phase 1/2, open-label,multicenter study of isatuximab in combination with cemiplimab in patients with lymphoma

Patients with relapsed or refractory lymphoma have limited treatment options, requiring newer regimens. In this Phase 1/2 study (NCT03769181), we assessed the safety, efficacy, and pharmacokinetics of isatuximab (Isa, anti-CD38 antibody) in combination with cemiplimab (Cemi, anti-programmed death-1 [PD-1] receptor antibody; Isa + Cemi) in patients with classic Hodgkin lymphoma (cHL), diffuse large B-cell lymphoma (DLBCL), and peripheral T-cell lymphoma (PTCL). In Phase 1, we characterized the safety and tolerability of Isa + Cemi with planned dose de-escalation to determine the recommended Phase 2 dose (RP2D). Six patients in each cohort were treated with a starting dose of Isa + Cemi to determine the RP2D. In Phase 2, the primary endpoints were complete response in Cohort A1 (cHL anti-PD-1/programmed death-ligand 1 [PD-L1] naïve), and objective response rate in Cohorts A2 (cHL anti-PD-1/PD-L1 progressors), B (DLBCL), and C (PTCL). An interim analysis was performed when the first 18 (Cohort A1), 12 (Cohort A2), 17 (Cohort B), and 11 (Cohort C) patients in Phase 2 had been treated and followed up for 24 weeks. Isa + Cemi demonstrated a manageable safety profile with no new safety signals. No dose-limiting toxicities were observed at the starting dose; thus, the starting dose of each drug was confirmed as the RP2D. Based on the Lugano 2014 criteria, 55.6% (Cohort A1), 33.3% (Cohort A2), 5.9% (Cohort B), and 9.1% (Cohort C) of patients achieved a complete or partial response. Pharmacokinetic analyses suggested no effect of Cemi on Isa exposure. Modest clinical efficacy was observed in patients with cHL regardless of prior anti-PD-1/PD-L1 exposure. In DLBCL or PTCL cohorts, interim efficacy analysis results did not meet prespecified criteria to continue enrollment in Phase 2 Stage 2. Isa + Cemi did not have a synergistic effect in these patient populations.