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Nivolumab-mediated PD-1 blockade is highly effective in many tumors with an acceptable toxicity profile [1,2,3].
We report a case of successful nivolumab treatment in a patient with HIV infection with CD4 counts persistently below 200/μL, and classic Hodgkin’s lymphoma (cHL) refractory to multiple chemotherapy regimens including both autologous stem cell transplant and bretuximab vedotin.
In February 2014, a 50-year-old man was diagnosed of cHL mixed cellularity, stage IIIBs, Epstein-Barr virus (EBV) related. The patient was affected by AIDS (pneumocystis infection during HIV) since 1994, refractory to different antiretroviral therapies (ART), complicated by HCV and HBV coinfection. He started treatment with adriblastine, dacarbazine, and bleomicine (ABD) removing vinblastine because of ART-related neuropathy. Interim PET showed a good response with 5-point Deauville Score (DS) = 3. Unfortunately, after 6 courses, the CT-PET documented a progressive disease (PD). BeGEV regimen (bendamustine, gemcitabine, vinorelbine, dexamethasone) was started, intended as a bridge to ASCT, but after three cycles CT-PET showed no response [4]. A third-line treatment with bleomicine, adriamicine, vincristine, ciclofosfamide, procarbazine, etoposide, and prednisone (BEACOPP) was administered for three cycles, finally resulting in a negative PET, so in September 2015 the patient underwent to ASCT with FEAM (fotemustine, etoposide, melphalan, cytarabine) conditioning regimen.
During the entire period of treatment, the HIV load was undetectable with a CD4 count persistently below 200/μL although the patient never stopped ART with emtricitabine/tenofovir disoproxil fumarate plus raltegravir. After 7 months from ASCT, the patient experienced a massive relapse with lung and bone involvement (stage IVB), refractory to both, a therapeutic regimen with cysplatinum and high-dose cytarabine plus dexamethasone (DHAP) (performed for 3 courses) as well as the anti-CD30 monoclonal antibody brentuximab vedotin (performed for 8 courses) [5]. The clinical conditions dramatically worsened and he had to be hospitalized for a severe pneumonia requiring systemic antibiotic and antifungal treatments, while a CT scan showed a new progression of disease.
CD4 count dropped to 58/μL. The patient was no longer able to tolerate further chemotherapy so we decided to offer him an anti-PD1 treatment (nivolumab 3 mg/kg every 2 weeks) [6, 7].
Already after the second administration, he had a remarkable improvement of performance status. After 6 courses, the restaging CT-PET documented a regression of all disease localization except for a new site of increased uptake localized on the left upper lung lobe subsequently interpreted as a pseudoprogression, which disappeared in the following controls. After 16 courses, CD4 counts increased to 290/μL and HIV load was still undetectable, while the performance status impressively recovered to ECOG = 0. No serious treatment-related adverse events were recorded, except for a grade 2 thrombocytopenia resolved with therapy delay.
Some experiences suggest that PD-1/PDL-1/PD-L2 immune inhibitory pathway could play a role in chronic HIV infection: checkpoint inhibitors could potentially enhance immune effector responses restoring virus-specific T cells [8].
References
Topalian SL, Hodi FS, Brahmer JR, Gettinger SN, Smith DC, McDermott DF, Powderly JD, Carvajal RD, Sosman JA, Atkins MB, Leming PD, Spigel DR, Antonia SJ, Horn L, Drake CG, Pardoll DM, Chen L, Sharfman WH, Anders RA, Taube JM, McMiller TL, Xu H, Korman AJ, Jure-Kunkel M, Agrawal S, McDonald D, Kollia GD, Gupta A, Wigginton JM, Sznol M (2012) Safety, activity, and immune correlates of anti–PD-1 antibody in cancer. N Engl J Med 366:2443–54. 5
Lipson EJ, Sharfman WH, Drake CG, Wollner I, Taube JM, Anders RA, Xu H, Yao S, Pons A, Chen L, Pardoll DM, Brahmer JR, Topalian SL (2013) Durable cancer regression off-treatment and effective reinduction therapy with an anti-PD-1 antibody. Clin Cancer Res 19:462–468
Ansell SM, Lesokhin AM, Borrello I, Halwani A, Scott EC, Gutierrez M, Schuster SJ, Millenson MM, Cattry D, Freeman GJ, Rodig SJ, Chapuy B, Ligon AH, Zhu L, Grosso JF, Kim SY, Timmerman JM, Shipp MA, Armand P (2015) PD-1 blockade with nivolumab in relapsed or refractory Hodgkin’s lymphoma. N Engl J Med 372:311–319
Santoro A, Mazza R, Pulsoni A, Re A, Bonfichi M, Zilioli VR, Salvi F, Merli F, Anastasia A, Luminari S, Annechini G, Gotti M, Peli A, Liberati AM, Di Renzo N, Castagna L, Giordano L, Carlo-Stella C (2016) Bendamustine in combination with gemcitabine and vinorelbine is an effective regimen as induction chemotherapy before autologous stem-cell transplantation for relapsed or refractory Hodgkin lymphoma: final results of a multicenter phase II study. J Clin Oncol 34(27):3293–3299
Younes A, Gopal AK, Smith SE, Ansell SM, Rosenblatt JD, Savage KJ, Ramchandren R, Bartlett NL, Cheson BD, de Vos S, Forero-Torres A, Moskowitz CH, Connors JM, Engert A, Larsen EK, Kennedy DA, Sievers EL, Chen R (2012) Results of a pivotal phase II study of brentuximab vedotin for patients with relapsed or refractory Hodgkin’s lymphoma. J Clin Oncol 30:2183–2189
Younes A, Santoro A, Shipp M, Zinzani PL, Timmerman JM, Ansell S, Armand P, Fanale M, Ratanatharathorn V, Kuruvilla J, Cohen JB, Collins G, Savage KJ, Trneny M, Kato K, Farsaci B, Parker SM, Rodig S, Roemer MGM, Ligon AH, Engert A (2016) Nivolumab for classical Hodgkin’s lymphoma after failure of both autologous stem-cell transplantation and brentuximab vedotin: a multicentre, multicohort, single-arm phase 2 trial. Lancet Oncol 17:1283–1294
Ansell SM, Lesokhin AM, Borrello I, Halwani A, Scott EC, Gutierrez M, Schuster SJ, Millenson MM, Cattry D, Freeman GJ, Rodig SJ, Chapuy B, Ligon AH, Zhu L, Grosso JF, Kim SY, Timmerman JM, Shipp MA, Armand P.N. PD-1 blockade with nivolumab in relapsed or refractory Hodgkin’s lymphoma. Engl J Med. 2015; 372(4):311–319
Velu V, Shetty RD, Larsson M, Shankar EM (2015) Role of PD-1 co-inhibitory pathway in HIV infection and potential therapeutic options. Retrovirology 12:14
Sandoval-Sus JD, Mogollon-Duffo F, Patel A, Visweshwar N, Laber DA, Kim R, Jagal MV (2017) Nivolumab as salvage treatment in a patient with HIV-related relapsed/refractory Hodgkin lymphoma and liver failure with encephalopathy. J Immunother Cancer 5:49
Chang E, Rivero G, Patel NR, Chiao EY, Lai S, Bajaj K, Mbue JE, Yellapragada SV (2018) HIV-related refractory Hodgkin lymphoma: a case report of complete response to nivolumab. Clin Lymphoma Myeloma Leuk 18(2):e143–e146
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Serrao, A., Canichella, M., De Luca, M.L. et al. Nivolumab as a safe and effective treatment in an HIV patient with refractory Hodgkin lymphoma. Ann Hematol 98, 1505–1506 (2019). https://doi.org/10.1007/s00277-018-3541-0
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DOI: https://doi.org/10.1007/s00277-018-3541-0