title: Rituximab, cyclophosphamide-fractionated, vincristine, doxorubicin and dexamethasone alternating with rituximab, methotrexate and cytarabine overcomes risk features associated with inferior outcomes in treatment of newly diagnosed, high-risk diffuse large B-cell lymphoma.
abstract: Subtypes of diffuse large B-cell lymphoma (DLBCL) that have inferior outcomes after front-line therapy with R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone) have been identified. While it is agreed that R-CHOP is probably not adequate in these patients, there is no standard treatment approach for patients with DLBCL with high-risk features. We present results of a retrospective cohort study of high-risk DLBCL (defined as having at least one unfavorable risk factor: non-germinal center [GC] subtype by immunohistochemistry [IHC], Ki-67 ≥ 80%, high International Prognostic Index [IPI], c-MYC rearrangement) treated with R-HCVAD/R-MTX-AraC (rituximab, cyclophosphamide-fractionated, vincristine, doxorubicin and dexamethasone alternating with rituximab, methotrexate and cytarabine; R-HCVAD) as front-line therapy. With a median follow-up of 25.3 months, the 3-year PFS and OS estimates are 79% (95% confidence interval [CI], 65-88%) and 76% (95% CI, 61-86%), respectively, which are higher than those for historical comparisons with R-CHOP data for high-risk patients. These data are in accord with other recent reports of dose-intense front-line therapy of high-risk DLBCL. This analysis represents the largest reported cohort of patients with DLBCL treated with R-HCVAD. These data suggest that R-HCVAD can overcome traditional poor risk features such as high IPI, high Ki-67 and non-GC IHC pattern. Future work will focus on identifying molecular markers for failure in patients with DLBCL treated with dose-intensive regimens.
authors.affiliation: Lymphoma Division, John Theurer Cancer Center, Hackensack University Medical Center , Hackensack, NJ , USA.
authors.forename: Anthony
authors.initials: A
authors.lastname: Mato
authors.forename: Tatyana
authors.initials: T
authors.lastname: Feldman
authors.forename: Tania
authors.initials: T
authors.lastname: Zielonka
authors.forename: Arun
authors.initials: A
authors.lastname: Singavi
authors.forename: Gabriella
authors.initials: G
authors.lastname: Gadaletta
authors.forename: Kathryn
authors.initials: K
authors.lastname: Waksmundzki
authors.forename: Pritish
authors.initials: P
authors.lastname: Bhattacharyya
authors.forename: Kar Fai
authors.initials: KF
authors.lastname: Chow
authors.forename: Xiao
authors.initials: X
authors.lastname: Yang
authors.forename: David
authors.initials: D
authors.lastname: Panush
authors.forename: Harry
authors.initials: H
authors.lastname: Agress
authors.forename: Maria
authors.initials: M
authors.lastname: Rosario
authors.forename: Christina
authors.initials: C
authors.lastname: Howlett
authors.forename: Andrew
authors.initials: A
authors.lastname: Pecora
authors.forename: Andre
authors.initials: A
authors.lastname: Goy
mesh_terms: D000328:Adult; D000368:Aged; D058846:Antibodies, Monoclonal, Murine-Derived / Q000009:adverse effects / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D003520:Cyclophosphamide / Q000009:adverse effects / Q000627:therapeutic use; D004317:Doxorubicin / Q000009:adverse effects / Q000627:therapeutic use; D006801:Humans; D016403:Lymphoma, Large B-Cell, Diffuse / Q000188:drug therapy* / Q000401:mortality; D008875:Middle Aged; D011241:Prednisone / Q000009:adverse effects / Q000627:therapeutic use; D012189:Retrospective Studies; D012307:Risk Factors; D000069283:Rituximab; D016896:Treatment Outcome; D014750:Vincristine / Q000009:adverse effects / Q000627:therapeutic use
chemical_list: D058846:Antibodies, Monoclonal, Murine-Derived; C571759:R-CHOP protocol; D000069283:Rituximab; D014750:Vincristine; D004317:Doxorubicin; D003520:Cyclophosphamide; D011241:Prednisone