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ABVD vs. Stanford V vs. MOPP-EBV-CAD in advanced Hodgkin's lymphoma.  Final results of the IIL HD9601 randomized trial

Reviewer: S. Jack Wei, MD
Abramson Cancer Center of the University of Pennsylvania
Ultima Vez Modificado: 5 de junio del 2004

Presenter: M. Federico
Presenter's Affiliation: Intergruppo Italiano Linfomi
Type of Session: Scientific

Background

• The standard treatment for advanced Hodgkin's lymphoma (HL) is ABVD chemotherapy
• 30% of patients with advanced HL do not respond to treatment with ABVD chemotherapy or subsequently relapse
• Recent studies have shown that Stanford V (SV) and MOPP-EBV-CAD (MEC) may result in higher cure rates including one report that found 3-year failure-free survival of 87% with Stanford V chemotherapy
• Previous studies of alternative regimens have not been performed in a prospective, randomized fashion

Materials and Methods

• From January 1996 to April 2000, 355 patients with stage IIB-IV HL were randomized to receive ABVD x 6 cycles (n=122), MEC x 6 cycles (n=106), or ABVD x 12 wks (n=107).  20 patients were excluded due to missing data, early withdrawal, or revised histology
• Patients were assessed for response after treatment and those with no response or progressive disease were treated with salvage chemotherapy; those with good partial response or complete response were evaluated for radiotherapy (RT)
• RT was delivered to residual disease in patients with partial responses or to sites of previously bulky disease (>= 6 cm)
• The principal end point was FFS with the study powered for expected 3-year FFS of 65% in the ABVD arm and 85% in the MEC and SV arms.
• Secondary endpoints included response rates, freedom from progression (FFP), and overall survival (OS)

Results

• Patient characteristics and risk factors including bulky disease, elevated LDH, anemia, and IPI >= 3 were well-balanced between all 3 groups
• Median follow-up was 56 months
• Radiotherapy was delivered to 62% in the ABVD arm, 47% in the MEC arm, and 66% in the SV arm
• Complete response was achieved in 89% (ABVD), 94% (MEC), and 76% (SV) (p<0.01)
• 5-year failure-free survival (FFS): 78% (ABVD) vs. 81% (MEC) vs. 51% (SV) (p<0.01)
• 5-year freedom from progression (FFP): 79% (ABVD) vs. 89% (MEC) vs. 55% (SV) (p<0.01)
• 5-year overall survival (OS): 90% (ABVD) vs. 89% (MEC) vs. 83% (SV) (p=0.16)
• Grade III-IV anemia: 0% (ABVD) vs. 23% (MEC) vs. 16%(SV)
• Grade III-IV leukopenia: 13% (ABVD) vs. 52% (MEC) vs. 31% (SV) (p<0.01)
• Grade III-IV thrombocytopenia: 0% (ABVD) vs. 23% (MEC) vs. 1% (SV)
• Grade III-IV infections: 1% (ABVD) vs. 14% (MEC) vs. 0% (SV) (p<0.01)
• Compared to previous studies showing higher rates of FFS with the SV regimen, this study had lower dose intensity of vincristine and a smaller percentage of patients receiving RT

Author's Conclusions

• ABVD and MEC are superior to SV in terms of response, FFS, and FFP when RT is optional
• No statistically significant difference in overall survival was seen between groups largely because of the high rate of salvage in patients receiving SV who failed
• Treatment with MEC requires less RT compared to ABVD and SV
• ABVD is less toxic than MEC and SV chemotherapy
• SV is less toxic than MEC

Clinical/Scientific Implications
The results of this study seem to show that ABVD and MEC chemotherapy result in superior outcome when RT is optional. In addition, while MEC is more acutely toxic, it results in less patients requiring RT due to higher rates of CR.  This may improve the long-term toxicity profile of these patients.  The rates of response seen with patients receiving SV are in conflict with previously published reports including those from Stanford and from ECOG.  This is likely due to the lower rates of patients receiving RT and lower dose intensity of vincristine in this study compared to previous studies.  While the results of this trial are intriguing, their applicability are unclear due to the less intense treatment received by patients in the SV.  Currently, a randomized trial is being conducted in the United States that directly compares the ABVD and SV regimens.  The SV used in the US trial is similar to the previous reports and results of this study will help clarify the overall effectiveness of SV chemotherapy.  In the meantime, ABVD remains the standard treatment for patients with advanced HL.

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