EPOCH-FR: A novel salvage regimen for patients with lymphoid malignancies being considered for reduced-intensity allogeneic hematopoietic stem cell transplantation.

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BlankEPOCH-FR: A novel salvage regimen for patients with lymphoid malignancies

being considered for reduced-intensity allogeneic hematopoietic stem cell

transplantation.

Sub-category: Allogeneic Bone Marrow

Category: Leukemia, Myelodysplasia, and Transplantation

Meeting: 2010 ASCO Annual Meeting

Citation: J Clin Oncol 28:7s, 2010 (suppl; abstr 6536)

Abstract No: 6536

Author(s): R. B. Salit, D. H. Fowler, W. H. , S. Z. Pavletic, K. Dunleavy,

F. Hakim, S. M. Steinberg, J. Odom, K. , M. R. Bishop; Experimental

Transplantation and Immunology Branch, National Cancer Institute, Bethesda, MD;

Metabolism Branch, National Cancer Institute, Bethesda, MD; Biostatistics and

Data Management Section, National Cancer Institute, Bethesda, MD

Abstract:

Background: There is no standard chemotherapy regimen for patients (pts) with

lymphoid malignancies being considered for reduced intensity allogeneic

hematopoietic stem cell transplantation (RI-alloHSCT). The ideal regimen would

result in disease control and recipient lymphocyte depletion and have limited

toxicity. We developed a novel regimen consisting of continuous infusion

etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin plus

fludarabine ± rituximab, depending on CD20+ expression (EPOCH-FR). Methods: 147

pts, median age 50 yrs (range 21-71), with high-risk lymphoid malignancies (47%

with chemo-resistant disease to last regimen, median 3 prior regimens [range

1-13]) were given EPOCH-FR (74% dose-adjusted) prior to RI-alloHSCT. Pts

received 1 (48%), 2 (21%), or 3 (31%) cycles of EPOCH- FR until they were

lymphodepleted (CD4+ count < 100/µl) or had progressive disease. Results:

Overall response rate (RR) was 41% (16% CR, 25% PR); 39% had SD. RR of

FCC/CLL>DLBCL/HL>TCL (p = 0.047). More EPOCH-FR cycles were associated with

higher RR (17% vs. 33% vs. 84%) (p < 0.0001). 17% of pts with chemo-resistant

disease had CR/PR. EPOCH- FR resulted in significant lymphodepletion

(pretreatment median CD3+ = 574/µl, CD4+ = 244/µl, and CD8+ = 249/µl vs.

posttreatment CD3+ = 184/µl, CD4+ = 97/µl and CD8+ = 68/µl (p < 0.0001). Pts

with greater lymphodepletion of CD3+ (p=0.038) and CD4+ (p=0.017) were more

likely to achieve CR/PR. Toxicity in 263 cycles included Grade 4

thrombocytopenia in 25%, neutropenia in 65%, and non-heme toxicity in 6%. Of 147

pts, 143 proceeded to RI-alloHSCT. Pts with greater lymphodepletion of CD3+ (p =

0.0007), CD4+ (p = 0.0004), and CD8+ (p = 0.0019) were more likely to achieve

full donor lymphoid chimerism by Day +14 post-transplant. Following transplant,

pts with CR/PR vs SD/PD to EPOCH-FR had median EFS = 77.4 vs. 4.8 mos (p <

0.0001) and OS = 98.5 vs. 16.2 mos (p = 0.0006) respectively. Conclusions:

EPOCH-FR safely provides disease response and lymphodepletion in pts with

lymphoid malignancies being considered for RI-alloHSCT.