Ibrutinib was highly active, associated with durable responses, and safe in pretreated patients with Waldenström's macroglobulinemia. MYD88 and CXCR4 mutation status affected responses to this drug. (Funded by Pharmacyclics and others; ClinicalTrials.gov number, NCT01614821.).

Plasmablastic lymphoma (PBL) is an aggressive lymphoma commonly associated with HIV infection. However, PBL can also be seen in patients with other immunodeficiencies as well as in immunocompetent individuals. Because of its distinct clinical and pathological features, such as lack of expression of CD20, plasmablastic morphology, and clinical course characterized by early relapses and subsequent chemotherapy resistance, PBL can represent a diagnostic and therapeutic challenge for pathologists and clinicians alike. Despite the recent advances in the therapy of HIV-associated and aggressive lymphomas, patients with PBL for the most part have poor outcomes. The objectives of this review are to summarize the current knowledge on the epidemiology, biology, clinical and pathological characteristics, differential diagnosis, therapy, prognostic factors, outcomes, and potential novel therapeutic approaches in patients with PBL and also to increase the awareness toward PBL in the medical community.

Bruton tyrosine kinase (BTK) inhibition is an effective treatment approach for patients with Waldenström macroglobulinemia (WM). The phase 3 ASPEN study compared the efficacy and safety of ibrutinib, a first-generation BTK inhibitor, with zanubrutinib, a novel, highly selective BTK inhibitor, in patients with WM. Patients with MYD88L265P disease were randomly assigned 1:1 to treatment with either ibrutinib or zanubrutinib. The primary endpoint was the proportion of patients achieving a complete or very good partial response (CR or VGPR) by independent review. Key secondary endpoints included major response rate (MRR), progression-free survival (PFS), duration of response (DOR), disease burden, and safety. A total of 201 patients were randomized, and 199 received ≥1 dose of study treatment. No patient achieved a CR. Twenty-nine (28%) zanubrutinib and 19 (19%) ibrutinib patients achieved a VGPR, a non-statistically significant difference (P = .09). MRRs were 77% and 78% , respectively. Median DOR and PFS were not reached; 84% and 85% of ibrutinib and zanubrutinib patients were progression-free at 18 months. Incidence of atrial fibrillation, contusion, diarrhea, peripheral edema, hemorrhage, muscle spasms, and pneumonia, as well as adverse events leading to treatment discontinuation, were all lower among zanubrutinib recipients. Incidence of neutropenia was higher with zanubrutinib, although grade ≥3 infection rates were similar in both arms (1.2 and 1.1 events/100 person-months). These results demonstrate that zanubrutinib and ibrutinib are highly effective in the treatment of WM, but zanubrutinib treatment was associated with a trend toward better response quality and less toxicity, particularly cardiovascular toxicity.

Key Points A subset of DHL patients may be cured, and some patients may benefit from intensive induction. Further investigations into the roles of SCT and novel agents are needed.

Purpose Breast implant–associated anaplastic large-cell lymphoma (ALCL) is a recently described clinicopathologic entity that usually presents as an effusion-associated fibrous capsule surrounding an implant. Less frequently, it presents as a mass. The natural history of this disease and long-term outcomes are unknown. Patients and Methods We reviewed the literature for all published cases of breast implant–associated ALCL from 1997 to December 2012 and contacted corresponding authors to update clinical follow-up. Results The median overall survival (OS) for 60 patients was 12 years (median follow-up, 2 years; range, 0-14 years). Capsulectomy and implant removal was performed on 56 of 60 patients (93%). Therapeutic data were available for 55 patients: 39 patients (78%) received systemic chemotherapy, and of the 16 patients (28%) who did not receive chemotherapy, 12 patients opted for watchful waiting and four patients received radiation therapy alone. Thirty-nine (93%) of 42 patients with disease confined by the fibrous capsule achieved complete remission, compared with complete remission in 13 (72%) of 18 patients with a tumor mass. Patients with a breast mass had worse OS and progression-free survival (PFS; P = .052 and P = .03, respectively). The OS or PFS were similar between patients who received and did not receive chemotherapy (P = .44 and P = .28, respectively). Conclusion Most patients with breast implant–associated ALCL who had disease confined within the fibrous capsule achieved complete remission. Proper management for these patients may be limited to capsulectomy and implant removal. Patients who present with a mass have a more aggressive clinical course that may be fatal, justifying cytotoxic chemotherapy in addition to removal of implants.

140-HELD-420 denotes that this patient was on 140 mg/d of ibrutinib prior to hospitalization that was held upon admission; he experienced worsening hypoxia after ibrutinib was held and required mechanical ventilation, following which he was restarted on 420 mg/d of ibrutinib and showed rapid improvement in oxygenation.

Plasmablastic lymphoma (PBL) is a distinct subtype of non-Hodgkin B-cell lymphoma, originally described with a strong predilection to the oral cavity of human immunodeficiency virus (HIV)-infected individuals. Data regarding patient age and gender, HIV status, initiation of and response to highly active antiretroviral therapy (HAART), tumor extent, pathology, treatment, and outcome were extracted from 112 cases of PBL identified in the literature. The median age at presentation was 38 years with a male predominance of 7:1, and the median CD41 count was 178 cells/mm 3 . PBL presented on average 5 years after diagnosis of HIV. Common primary sites of presentation included the oral cavity, gastrointestinal tract, and lymph nodes. Most cases presented with either stage I or stage IV disease. There was a variable expression of B-cell markers in tumor cells, but plasma cell markers were expressed in all cases. EBV was detected in 74%. Chemotherapy was used to treat 55% patients and was combined with radiotherapy in 21% cases. Complete response was obtained in 66% of treated cases; the majority of these responses were seen after CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone). The refractory/relapsed disease rate was 54%. Death occurred in 53% of patients, with a median overall survival of 15 months. Sex, CD41 count, viral load, clinical stage, EBV status, primary site of involvement, and use of CHOP failed to show an association with survival. PBL is an aggressive B-cell lymphoma that presents in both oral and extra-oral sites of chronically HIV-infected immunosuppressed young men. Am. J. Hematol. 83:804-809, 2008. V

Plasmablastic lymphoma (PBL) is a distinct variant of diffuse large B-cell lymphoma initially described in HIV-positive patients. Several studies have reported the occurrence of PBL in HIV-negative patients, but comparative data are lacking. The goal of this study was to compare the characteristics of HIV-positive and HIV-negative patients with PBL. A MEDLINE search was undertaken through August 2009 for cases of PBL in HIV-positive and HIV-negative patients. Cases were identified and clinicopathological data were gathered. χ(2) was used to compare categorical and t-test to compare continuous variables between groups. Calculated Kaplan-Meier survival estimates were compared using the log-rank test. Cox proportional-hazard regression was used for multivariate analysis. From 228 identified cases of PBL, 157 were HIV-positive and 71 HIV-negative. HIV-positive patients were younger, and more likely to be men, present with oral involvement, respond to chemotherapy, and express CD20, CD56, and EBV-encoded RNA than HIV-negative patients. In univariate analysis, age ≥60, advanced stage, bone marrow involvement, no chemotherapy, Ki-67 expression >80%, and HIV-negative status were associated with worse overall survival. In multivariate analysis, advanced stage and no chemotherapy were independent adverse prognostic factors. In conclusion, HIV-positive and HIV-negative patients with PBL have different clinicopathological characteristics, including a better response to chemotherapy and longer survival in HIV-positive patients.