Dose Dense and Dose Intense ABVD (dd-di ABVD) in Advanced and Intermediate-Stage Hodgkin’s Lymphoma (HL).
Authors: Russo Filippo , Corazzelli Gaetano , Frigeri Ferdinando , Marcacci Gianpaolo , Pinto Antonio 
Published: October 2019

ABVD is still considered the standard therapy for HL being a good balance of efficacy and tolerability. Here we report the 3-yr results of a phase 2 study which explore the possibility to ameliorate the performance of this (g)old schedule. Modifications of the standard ABVD and strategy concepts :

Each patient received a total of 6 cycles For advanced stage, Adriamycin (ADM) was escalated from 50 to 70 mg/m2 in the cycles 1,2,3,4. Intermediate stage patients (pts) were treated without the dose escalation of ADM. The cumulative doses of ADM were 380 (advanced-) and 300 mg/m2 (intermediate-stage). The inter-cycle period was shortened from 28 to 21 days for all 6 cycles; the 4 drugs were delivered at d 1 and 11 of each cycle. Primary G-CSF was given from d4 to d8, and from d14 to d18 of each cycle. The therapy program was driven by interim-FDG-PET. Normalisation of PET at the end of 2nd cycles was indicator of early complete response (CR), while the persistence of PET+ lesion(s) at the end of the 4th cycle was indicator of failure and consequently the treatment was shift to a salvage therapy Consolidation Radiotherapy was reserved only for bone lesions.

From June 2004 to May 2006 fifty-eight pts were enrolled (Tab 1). On 20th August 2007 all patients have performed the interim-PET and 54/58 pts completed the treatment. Administered RDIs ranged between 1.10 to 1.44 (median 1.34) for DD-DI ABVD, and 1.18 to 1.34 (median 1.24) for DD ABVD. Hematologic toxicity was moderate and self-limiting with grade 3 or 4 neutropenia and anemia occuring in less than 20% of courses. Non-hematologic toxicity was generally mild to moderate. A limited number of G3-G4 reversible events determined the need for intervention (RBC’s trasfusions) or hospitalisation (pulmonary infections, GI and respiratory tracts, and neurological effects).The majority of pts presented a mild to moderate palmar-plantar erythrodysesthesia. Early cardiac toxicity was very mild. 55/ 58 obtained the early CR (95%) and 54/ 54 the CR (100%); a 60-yr old man died of pneumonia a month after the end of the last cycle still being in CR while one-site relapse occurred in a 27-yr old girl at ten month from the end of therapy. All the other pts are alive and disease-free. (tab 2 and fig 1). DD-DI ABVD and DD ABVD are feasible, well tolerated and highly active in advanced and intermediate HL: at 3 years from the beginning of the study these schedules confirm to be a promising strategy for optimal long-term results.

tab 1 Presentation features N % GHSG NCI total 58 100% N % N % advanced 36 62% 51 88% intermediate 22 38% 7 12% male 21 36% age>45-yr 6 10% bulky 21 36% stage IV 17 29% B symptoms 37 64% extranodal 20 35% ESR >50 mm 30 52% LDH ratio>1 25 43% IPS>3 20 35% N sites>3 42 72% Tab 2 Response and Survival Data N early CR CR TRM Relapse 3-yr EFS 3-yr OS median f-up 17 mos 58 (100%) 55 (95%) 54/54 (100%) 1 (2%) 1 (2%) 98% 98% GHSG advanced 36 35 (97%) 33/33 (100%) 100% 97% intermediate 22 20 (91%) 21/21 (100%) 95% 100% NCI advanced 51 49 (96%) 48/48 (100%) 98% 98% intermediate 7 6 (86%) 6/6 (100%) 100% 100% Fig. 1 Fig. 1.