R-GIFOX Tested in Aggressive/Progressive Lymphomas

[Guest guest]

[No CLL patients here, but perhaps for aggressive CLL or Richter's?]

Gemcitabine, Ifosfamide, Oxaliplatin and Rituximab

(R-GIFOX), a New

Effective Cytoreductive/Mobilizing Salvage Regimen for

Relapsed and

Refractory Aggressive Non-Hodgkin's Lymphoma: Results of a

Pilot Study.

Session Type: Poster Session 98-I

Gaetano Corazzelli, Filippo Russo, Gaetana Capobianco,

Gianpaolo Marcacci,

Paola Della Cioppa, Pinto (Intr. by Felicetto

Ferrara) Hematology

Oncology Unit, INT, Fondazione Pascale, IRCCS, Naples,

Italy

Objective: In this pilot study we evaluated the clinical

activity, toxicity

and mobilizing capacity of a new short-course (bi-weekly),

dose intensive,

cytoreductive/mobilizing salvage regimen (R-GIFOX)

combining the

cross-synergistic agents Gemcitabine (G), Ifosfamide (Ifo),

Oxaliplatin (Ox)

and Rituximab ®, in patients with relapsed and refractory

CD20+ NHL.

Based on the predicted clinical activity, tolerability and

synergy among

drugs, the R-GIFOX regimen may offer an effective and less

toxic alternative

to Cisplatin/ARA-C-based salvage regimens, also for

patients aged or unfit

for high-dose procedures.

Patients and methods: Patients were scheduled to receive

three courses of

therapy followed by mobilization and ASCT or three more

courses if

ineligible for ASCT.

Therapy was delivered on a compassionate basis after

written informed

consent. R-GIFOX consisted of R (375 mg/m2, d 1), G (1000

mg/m2, d 2), Ox

(130 mg/m2, d 3) and Ifo (5 g/m2, d 3), as a 24-hour single

infusion in

patients aged ? 65 years, or fractionated over 3 days (dd

3-5) in older

patients.

Treatment was given every two weeks with G-CSF support (5

mcg/kg/day, dd

6-11; 10 mcg/kg/day at the 3rd course for stem cells

mobilization).

Responses were evaluated after three courses by the

integrated FDG-PET/IWC

criteria, and reassessed at the end of the entire program.

Results: Fourteen patients (median age 63 years, range

37-78 years) with

relapsed (n = 9) or primary progressive (n = 5) aggressive

[diffuse large

cell (n=7), mantle cell (n=4), follicular G3b (n=3)],

advanced (stage IV =

71%), poor risk (IPI 3-5 = 50%; median number of previous

therapy=2, r 1-4)

NHL, were accrued.

Forty-nine total courses were delivered (median 4, range

1-6); thirteen

patients completed at least 3 courses of therapy and were

evaluable for

response.

Actual dose intensity of the first 3 courses was 81%,

83.5%, and 86.5% for

G, Ifo and Ox, respectively. CTCAE v3.0 G3/G4

thrombocytopenia was present

in 26 % of courses, G3/G4 neutropenia in 22%; febrile

neutropenia and

infections in 8% and 6% of cycles, respectively.

The ORR assessed after three courses of R-GIFOX was 77%,

with 7 complete

responses (54%; CR=5; CRu=2) and 3 partial; CRu converted

to CR at BM biopsy

after 6 courses.

According to age, the ORR was 67% (4 CR, 2 PR) and 80% (3

CR, 1 PR) for

patients aged ? 65 years and those older, respectively.

According to disease

status, the ORR was 40% (1 CR, 1 PR) and 89% (6 CR, 2 PR)

for primary

refractory and relapsed patients, respectively. Among CRs

no patient has

relapsed at a median time of 5 months (range, 2+ - 10+).

Effective CD34+ cell mobilization was obtained in 4 out of

6 eligible

patients and 2 already received ASCT. Failure free survival

was 79.6%. In

mantle cell lymphoma 2 CRs and 1 PR were obtained,

including 2 molecular

remissions (BM, PB).

Conclusions: Based on the results of

this pilot study,

R-GIFOX was feasible, tolerable, effective and able to

mobilize peripheral

stem cells in patients with reccurrent aggressive NHL.

It enabled the achievement of effective dose-intensities

and high response

rates also in the older patients.

Finally, the R-GIFOX regimen showed clinical activity also

in 'difficult'

histotypes such as mantle cell lymphomas.

Abstract #940 appears in Blood, Volume 106, issue 11,

November 16, 2005