A dose-dense short-term therapy for human immunodeficiency virus/acquired immunodeficiency syndrome patients with high-risk Burkitt lymphoma or high-grade B-cell lymphoma: safety and efficacy results of the "CARMEN" phase II trial.
Acquired Immunodeficiency Syndrome
/ complications
Adult
Antimetabolites, Antineoplastic
/ administration & dosage
Antineoplastic Combined Chemotherapy Protocols
/ administration & dosage
Antiviral Agents
/ administration & dosage
Burkitt Lymphoma
/ complications
Carmustine
/ administration & dosage
Cytarabine
/ administration & dosage
Etoposide
/ administration & dosage
Female
HIV Infections
/ complications
Hematopoietic Stem Cell Transplantation
/ adverse effects
Humans
Lymphoma, B-Cell
/ complications
Male
Melphalan
/ administration & dosage
Middle Aged
Transplantation, Autologous
/ adverse effects
MYC
Burkitt lymphoma
Human Immunodeficiency Virus
central nervous system prophylaxis
double-hit lymphoma
high-grade B-cell lymphoma
Journal
British journal of haematology
ISSN: 1365-2141
Titre abrégé: Br J Haematol
Pays: England
ID NLM: 0372544
Informations de publication
Date de publication:
01 2021
01 2021
Historique:
received:
28
07
2020
accepted:
02
09
2020
pubmed:
22
10
2020
medline:
27
4
2021
entrez:
21
10
2020
Statut:
ppublish
Résumé
A few prospective trials in HIV-positive patients with Burkitt lymphoma (BL) or high-grade B-cell lymphoma (HGBL) have been reported. Investigated therapies have shown good efficacy but relevant safety problems, with high rates of interruptions, severe mucositis, septic complications, and fungal infections. Here, we report the results of a multicentre phase II trial addressing a new dose-dense, short-term therapy aimed at maintaining efficacy and improving tolerability. The experimental programme included a 36-day polychemotherapy induction followed by high-dose cytarabine-based consolidation and response-tailored BEAM (carmustine, etoposide, cyatarabine, and melphalan)- conditioned autologous stem cell transplantation (ASCT). This therapy would be considered active if ≥11 complete remissions (CR) after induction (primary endpoint) were recorded among 20 assessable patients. HIV-positive adults (median age 42, range 26-58; 16 males) with untreated BL (n = 16), HGBL (n = 3) or double-hit lymphoma (n = 1) were enrolled. All patients had high-risk features, with meningeal and bone marrow infiltration in five and nine patients respectively. The experimental programme was safe and active in a multicentre setting, with only two episodes of grade 4 non-haematological toxicity (hepatotoxicity and mucositis), and no cases of systemic fungal infections; two patients died of toxicity (bacterial infections). Response after induction (median duration: 47 days; interquartile range 41-54), was complete in 13 patients and partial in five [overall response rate = 90%; 95% confidence interval (CI) = 77-100]. All responders received consolidation, and five required autologous stem cell transplant. At a median follow-up of 55 (41-89) months, 14 patients are relapse-free and 15 are alive, with a five-year progression-free survival and an overall survival of 70% (95% CI = 60-80%) and 75% (95% CI = 66-84) respectively. No patient with cerebrospinal fluid (CSF)/meningeal lymphoma experienced central nervous system recurrence. With respect to previously reported regimens, this programme was delivered in a shorter period, and achieved the main goal of maintaining efficacy and improving tolerability.
Substances chimiques
Antimetabolites, Antineoplastic
0
Antiviral Agents
0
Cytarabine
04079A1RDZ
Etoposide
6PLQ3CP4P3
Melphalan
Q41OR9510P
Carmustine
U68WG3173Y
Types de publication
Clinical Trial, Phase II
Journal Article
Multicenter Study
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
119-128Subventions
Organisme : Rete Oncologica Lombarda
ID : Bando ROL/REL 2010
Commentaires et corrections
Type : CommentIn
Informations de copyright
© 2020 British Society for Haematology and John Wiley & Sons Ltd.
Références
Alderuccio JP, Olszewski AJ, Danilov A, Jagadeesh D, Sperling A, Kim SK, et al. Characteristics and outcomes of HIV-related Burkitt lymphoma (HIV-BL) in the post-rituximab era across 30 US cancer centers. Haematologica. 2020, abstract #S239.105: 95
Barnes JA, Lacasce AS, Feng Y, Toomey CE, Neuberg D, Michaelson JS, et al. Evaluation of the addition of rituximab to CODOX-M/IVAC for Burkitt's lymphoma: a retrospective analysis. Ann Oncol. 2011;22:1859-64.
Carrillo-Cruz E, Marin-Oyaga VA, Sole Rodriguez M, Borrego-Dorado I, de la Cruz Vicente F, Quiroga Cantero E, et al. Role of 18F-FDG-PET/CT in the management of Burkitt lymphoma. Eur J Haematol. 2015;94:23-30.
Cheson BD, Pfistner B, Juweid ME, Gascoyne RD, Specht L, Horning SJ, et al. Revised response criteria for malignant lymphoma. J Clin Oncol. 2007;25:579-86.
Cook JR, Goldman B, Tubbs RR, Rimsza L, Leblanc M, Stiff P, et al. Clinical significance of MYC expression and/or "high-grade" morphology in non-Burkitt, diffuse aggressive B-cell lymphomas: a SWOG S9704 correlative study. Am J Surg Pathol. 2014;38:494-501.
Cortes J, Thomas D, Rios A, Koller C, O'Brien S, Jeha S, et al. Hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone and highly active antiretroviral therapy for patients with acquired immunodeficiency syndrome-related Burkitt lymphoma/leukemia. Cancer. 2002;94:1492-9.
Di Nicola M, Carlo-Stella C, Mariotti J, Devizzi L, Massimino M, Cabras A, et al. High response rate and manageable toxicity with an intensive, short-term chemotherapy programme for Burkitt's lymphoma in adults. Br J Haematol. 2004;126:815-20.
Dunleavy K, Pittaluga S, Shovlin M, Steinberg SM, Cole D, Grant C, et al. Low-intensity therapy in adults with Burkitt's lymphoma. N Engl J Med. 2013;369:1915-25.
Ferreri AJ, Bruno Ventre M, Donadoni G, Cattaneo C, Fumagalli L, Foppoli M, et al. Safety and activity of a new intensive short-term chemoimmunotherapy in HIV-positive patients with Burkitt lymphoma. Br J Haematol. 2012;159:252-5.
Galicier L, Fieschi C, Borie R, Meignin V, Daniel MT, Gerard L, et al. Intensive chemotherapy regimen (LMB86) for st jude stage IV AIDS-related burkitt lymphoma/leukemia: a prospective study. Blood. 2007;110:2846-54.
Kluin PM, Harris NL, Stein H, Leoncini L, Campo E, Jaffe ES, et al. High-grade B-cell lymphoma. In: Swerdlow SH, Campo E, Harris NL, Jaffe ES, Pileri SA, Stein H, et al., editors. WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues. Lyon: IARC, 2017; p. 335-41.
Lim ST, Karim R, Tulpule A, Nathwani BN, Levine AM. Prognostic factors in HIV-related diffuse large-cell lymphoma: Before versus after highly active antiretroviral therapy. J Clin Oncol. 2005;23:8477-82.
Montoto S, Wilson J, Shaw K, Heath M, Wilson A, McNamara C, et al. Excellent immunological recovery following CODOX-M/IVAC, an effective intensive chemotherapy for HIV-associated burkitt's lymphoma. AIDS (London, England). 2010;24:851-6.
Noy A, Lee JY, Cesarman E, Ambinder R, Baiocchi R, Reid E, et al. AMC 048: Modified CODOX-M/IVAC-rituximab is safe and effective for HIV-associated burkitt lymphoma. Blood. 2015;126:160-6.
Oosten LEM, Chamuleau MED, Thielen FW, de Wreede LC, Siemes C, Doorduijn JK, et al. Treatment of sporadic burkitt lymphoma in adults, a retrospective comparison of four treatment regimens. Ann Hematol. 2018;97:255-66.
Oriol A, Ribera JM, Brunet S, del Potro E, Abella E, Esteve J. Highly active antiretroviral therapy and outcome of AIDS-related burkitt's lymphoma or leukemia. Results of the PETHEMA-LAL3/97 study. Haematologica. 2005;90:990-2.
Oriol A, Ribera JM, Bergua J, Gimenez Mesa E, Grande C, Esteve J, et al. High-dose chemotherapy and immunotherapy in adult burkitt lymphoma: Comparison of results in human immunodeficiency virus-infected and noninfected patients. Cancer. 2008;113:117-25.
Riad R, Omar W, Sidhom I, Zamzam M, Zaky I, Hafez M, et al. False-positive F-18 FDG uptake in PET/CT studies in pediatric patients with abdominal burkitt's lymphoma. Nucl Med Commun. 2010;31:232-8.
Rodrigo JA, Hicks LK, Cheung MC, Song KW, Ezzat H, Leger CS, et al. HIV-associated burkitt lymphoma: Good efficacy and tolerance of intensive chemotherapy including CODOX-M/IVAC with or without rituximab in the HAART era. Adv Hematol. 2012;2012:735392.
Roschewski M, Dunleavy K, Abramson JS, Powell BL, Link BK, Patel P, et al. Multicenter study of risk-adapted therapy with dose-adjusted EPOCH-R in adults with untreated Burkitt lymphoma. J Clin Oncol. 2020;38(22):2519-29.
Sparano JA, Lee JY, Kaplan LD, Levine AM, Ramos JC, Ambinder RF, et al. Rituximab plus concurrent infusional EPOCH chemotherapy is highly effective in HIV-associated B-cell non-Hodgkin lymphoma. Blood. 2010;115(15):3008-16.
Kluin PM, Harris NL, Stein H, Leoncini L, Raphael M, Campo E, et al. B-cell lymphoma, unclassifiable, with features intermediate between diffuse large B-cell lymphoma and Burkitt lymphoma. In: SH Swerdlow, E Campo, NL Harris, ES Jaffe, SA Pilri, H Stein, J Thiele, & JW Vardiman, editors. WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues. Lyon: IARC. 2008; p. 265-6.
Trotti A, Colevas AD, Setser A, Rusch V, Jaques D, Budach V, et al. CTCAE v3.0: Development of a comprehensive grading system for the adverse effects of cancer treatment. Semin Radiat Oncol. 2003;13:176-81.
Wang ES, Straus DJ, Teruya-Feldstein J, Qin J, Portlock C, Moskowitz C, et al. Intensive chemotherapy with cyclophosphamide, doxorubicin, high-dose methotrexate/ifosfamide, etoposide, and high-dose cytarabine (CODOX-M/IVAC) for human immunodeficiency virus-associated burkitt lymphoma. Cancer. 2003;98:1196-205.