Rituximab plus liposomal doxorubicin in HIV-infected patients with KSHV-associated multicentric Castleman disease

Uldrick, Thomas S.; Polizzotto, Mark N.; Aleman, Karen; Wyvill, Kathleen M.; Marshall, Vickie; Whitby, Denise; Wang, Victoria; Pittaluga, Stefania; O’Mahony, Deirdre; Steinberg, Seth M.; Little, Richard F.; Yarchoan, Robert

doi:10.1182/blood-2014-07-586800

Cited by 107 publications

(86 citation statements)

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“…by guest www.bloodjournal.org From or without HIV 9,32,33,35 However, although over half of our patients who were treated with rituximab or rituximab-based therapy had a response, only 20% achieved a CR; this percentage is much lower than that reported in the literature for patients with HHV-8-associated MCD (84%). 9 Siltuximab effectively controlled and improved the clinical manifestations and PFS in iMCD patients, even among those for whom rituximab failed, and the patients' mean response rate to siltuximab was significantly higher than that for rituximab or rituximab-based therapy and chemotherapy. Of note, the ;75% response rate in our series is much higher than the 34% response rate for siltuximab that was observed in the only randomized controlled trial of iMCD.…”

Section: Discussioncontrasting

confidence: 51%

“…9,11,32,33 In UCD, surgical complete resection is found to be the best first-line treatment. 11 In UCD patients refractory to surgical resection or inoperable, rituximab or radiotherapy can be effective.…”

Section: Discussionmentioning

confidence: 99%

“…HHV-8 status was determined based on the results of latency-associated nuclear antigen immunocytochemistry (27 cases) and polymerase chain reaction for HHV-8 of peripheral blood (4 cases) in iMCD during active disease; 18 patients with HIV-/HHV-8-positive MCD were previously studied by the National Cancer Institute as described elsewhere (protocol #NCT00099073). 9 A dose of 11 mg/kg siltuximab was administered intravenously every 3 weeks per protocol or every 6 weeks at the investigator's discretion. Patients received 375 mg/m 2 rituximab IV weekly for 4 weeks.…”

Section: Methodsmentioning

confidence: 99%

“…Complete surgical resection is the primary treatment modality for UCD, 11,12 but unresectable UCD cases are generally treated like iMCD cases. HHV-8-associated MCD is often well controlled with CD20 1 -depletion therapy using rituximab 9,10 ; antivirals and cytotoxic chemotherapy drugs may be added to the treatment regimen for refractory patients. Tocilizumab, which targets the IL-6 receptor, was approved for iMCD in Japan in 2005, and since then, it has been used as an off-label regimen around the world.…”

Section: Introductionmentioning

confidence: 99%

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Clinical and pathological characteristics of HIV- and HHV-8–negative Castleman disease

Cortes³

et al. 2017

Blood

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Section: Discussioncontrasting

confidence: 51%

Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Clinical and pathological characteristics of HIV- and HHV-8–negative Castleman disease

Cortes³

et al. 2017

Blood

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156

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“…A short course of valganciclovir (e.g., 3 months) may be useful to control HHV8 replication until the patient's immune system has been partially reconstituted [17]. Finally if the patient relapses rituximab may be used again with high salvage rates [22,23].…”

Section: Hiv/hhv-8 Positive Multicentric Castleman Diseasementioning

confidence: 99%

Role of Allogeneic Stem Cell Transplant in Chronic Lymphocytic Leukemia and its Implications in Current Era

Socola¹

2017

J Leuk

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Assessment of the Safety of Pembrolizumab in Patients With HIV and Advanced Cancer—A Phase 1 Study

et al. 2019

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; for the Cancer Immunotherapy Trials Network (CITN)-12 Study Team IMPORTANCE Anti−PD-1 (anti−programmed cell death 1) and anti−PD-L1 (anti−programmed cell death ligand 1) regimens are preferred therapies for many cancers, including cancers associated with HIV. However, patients with HIV were excluded from most registered trials. OBJECTIVE The primary objective was to evaluate the safety of pembrolizumab in people with HIV and advanced cancer; the secondary objective was to evaluate tumor responses. DESIGN, SETTING, AND PARTICIPANTS Open-label, nonrandomized, phase 1 multicenter study conducted at 7 Cancer Immunotherapy Trials Network sites. Patients with HIV and advanced cancer as well as a CD4 count greater than or equal to 100 cells/μL, antiretroviral therapy (ART) for 4 or more weeks, and an HIV viral load of less than 200 copies/mL were eligible. Exclusion criteria included uncontrolled hepatitis B or C infection, active immunosuppressive therapy, or a history of autoimmune disease requiring systemic therapy. INTERVENTIONS Pembrolizumab, 200 mg, administered intravenously every 3 weeks for up to 35 doses in 3 CD4 count−defined cohorts. Participants continued ART. MAIN OUTCOMES AND MEASURES Safety and tolerability were assessed using current NCI Common Terminology Criteria for Adverse Events. Immune-related adverse events grade 2 or higher were considered immune-related events of clinical interest (irECI). Tumor responses were evaluated using standard tumor-specific criteria. RESULTS Thirty participants (28 men and 2 women; median [range] age, 57 [39-77] years) were enrolled from April 2016 through March 2018; 6 had Kaposi sarcoma (KS), 5 had non-Hodgkin lymphoma (NHL), and 19 had non−AIDS-defining cancers. Safety was observed over 183 cycles of treatment with pembrolizumab. Most treatment-emergent adverse events at least possibly attributed to pembrolizumab were grade 1 or 2 (n = 22), and 20% (n = 6) were grade 3. The irECI included hypothyroidism (6 participants), pneumonitis (3 participants), rash (2 participants), an elevated aminotransferase/alanine aminotransferase level (1 participant), and a musculoskeletal event (1 participant). One participant with pretreatment KS herpesvirus (KSHV) viremia developed a polyclonal KSHV-associated B-cell lymphoproliferation and died. HIV was controlled in all participants. Increases in CD4 count were not statistically significant (median increase, 19 cells/μL; P = .18). Best tumor responses included complete response (lung, 1 patient), partial response (NHL, 2 patients), stable disease for 24 weeks or more (KS, 2 patients), stable disease for less than 24 weeks (15 patients), and progressive disease (8 patients); 2 patients were not evaluable. CONCLUSIONS AND RELEVANCE Pembrolizumab has acceptable safety in patients with cancer, HIV treated with ART, and a CD4 + T-cell count of greater than 100 cells/μL but may be associated with KSHV-associated B-cell lymphoproliferation. Clinical benefit was noted in lung cancer, NHL, and KS. Anti−PD-1 therapy is appropriate for US ...

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Rituximab plus liposomal doxorubicin in HIV-infected patients with KSHV-associated multicentric Castleman disease

Abstract: Key Points Rituximab plus liposomal doxorubicin is active and tolerated in patients with symptomatic KSHV-associated multicentric Castleman disease. This is a safe and effective initial regimen for concurrent symptomatic KSHV-associated multicentric Castleman disease and Kaposi sarcoma.

Cited by 107 publications

References 66 publications

Clinical and pathological characteristics of HIV- and HHV-8–negative Castleman disease

Clinical and pathological characteristics of HIV- and HHV-8–negative Castleman disease

Role of Allogeneic Stem Cell Transplant in Chronic Lymphocytic Leukemia and its Implications in Current Era

Assessment of the Safety of Pembrolizumab in Patients With HIV and Advanced Cancer—A Phase 1 Study

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