PET-guided treatment de-escalation feasible in Hodgkin lymphoma
medwireNews: A negative positron emission tomography (PET) scan after initial treatment with BEACOPP in escalated doses identifies Hodgkin lymphoma patients suitable for a reduction in the total number of cycles needed, HD18 trial data show.
“As a result from the reduced treatment intensity, the incidence of severe adverse events was significantly reduced and overall survival was significantly improved,” report Peter Borchmann (University Hospital of Cologne, Germany) and co-investigators in The Lancet.
Furthermore, “a positive PET scan after two cycles [PET-2] of eBEACOPP [escalated bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone] does not imply the need for intensification of chemotherapy, as reflected by the excellent progression-free survival [PFS] of patients with positive PET-2 regardless of treatment group,” they add.
Specifically, the 5-year PFS was 89.7% in the 217 advanced Hodgkin lymphoma patients with a positive scan after two cycles of eBEACOPP who were randomly assigned to receive six additional cycles of standard eBEACOPP and 88.1% in the 217 PET-2-positive patients randomly assigned to six additional cycles of eBEACOPP with rituximab.
Estimated 5-year overall survival (OS) was 96.4% and 93.9%, respectively, and the researchers observed a similarly high level of tumor control following a protocol amendment approximately 3 years into the 6-year recruitment period, which reduced standard therapy to six cycles of BEACOPP in total.
Patients with positive PET-2 who received six cycles of eBEACOPP had a 3-year PFS of 92.0% and 3-year OS of 98.0%, which was accompanied by an improved safety profile compared with eight cycles of eBEACOPP.
“We can thus safely recommend using only six cycles of eBEACOPP for patients with positive PET-2,” Borchmann et al remark.
For the 1005 patients with a negative PET-2, 5-year PFS was 90.8% among those randomly assigned to standard therapy with either eight or six cycles of eBEACOPP (n=504) and 92.2% among those randomly assigned to experimental treatment with four cycles of eBEACOPP (n=501). The 95% confidence interval for the difference between the two treatment regimens ranged from –2.7% to 5.4%, which met the predefined criteria for noninferiority, set at a maximum absolute difference of 6%.
Overall survival among PET-2-negative patients was also similar between the two treatment arms, with 5-year estimates of 95.4% and 97.7% in the standard and experimental groups, respectively.
In addition, the experimental four-cycle eBEACOPP regimen was associated with lower rates of severe infections (8% of 498 vs 15% of 502) and organ toxicities (8 vs 18%) than the eight- or six-cycle regimens, as well as no treatment-related deaths, compared with six in the PET-negative patients who received standard treatment.
Borchmann and team conclude: “PET-2-guided de-escalation has substantially reduced the treatment-related risks and at the same time improved the overall survival for early-responding patients.”
They add: “We therefore strongly recommend this PET-2-guided treatment strategy for patients with advanced-stage Hodgkin’s lymphoma.”
Commenting on the findings, Maja Maraldo, from the University of Copenhagen in Denmark, says that the HD18 trial “clearly demonstrates” that the addition of rituximab to standard treatment does not improve outcomes for PET-2 positive patients and that four cycles of eBEACOPP is equivalent to six or eight cycles, “which is a very important result for approximately half of advanced-stage patients.”
However, she questions whether the findings among patients with negative PET-2, ie, those with a Deauville score of 1–2, can be extended to those with a Deauville score of 3 or even 4 when four cycles of eBEACOPP are given upfront.
Maraldo concludes: “These questions should be formally tested, as the medical community is now left to speculate whether the maximum effect of upfront eBEACOPP is achieved with only four cycles.
“If so, the reluctance to use eBEACOPP owing to its toxicity profile might then be offset by the much increased efficacy and reduced treatment time as compared with doxorubicin, bleomycin, vinblastine, and dacarbazine.”
By Laura Cowen
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