What are the salvage chemotherapy regimens used in the treatment of DLBCL?

Updated: Jun 12, 2019
  • Author: Shipra Gandhi, MBBS; Chief Editor: Emmanuel C Besa, MD  more...
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Answer

There are a vast number of regimens used in the treatment of patients with relapsed/refractory DLBCL, and they are primarily based on non–cross-resistant chemotherapy agents to those used in the frontline setting plus/minus rituximab. The goal of salvage regimens is to achieve maximum tumor-burden cytoreduction in preparation for HDC-ASCS. The current salvage regimens available for refractory/relapsed DLBCL have been evaluated in phase II studies. Investigators have also tested the efficacy of adding rituximab to established salvage regimens and compared them with pre-rituximab historical controls. Several chemotherapy regimens have been used in case of disease relapse, as follows:

  • DHAP (dexamethasone, high-dose cytarabine [Ara-C], and cisplatin [Platinol])

  • ESHAP (etoposide, methylprednisolone, high-dose cytarabine, and cisplatin)

  • MIME (mesna, ifosfamide, methotrexate, and etoposide)

  • IMVP-16 (ifosfamide, methotrexate, and etoposide [VP-16])

The only randomized phase III trial that compared established salvage regimens in combination with rituximab (R-ICE vs R-DHAP) was the ongoing CORAL study. [118] Recently, the investigators reported an interim analysis of 200 patients enrolled that demonstrated factors affecting EFS include second-line age-adjusted IPI (aaIPI) of 0-1 (39% vs 56% P =.0084), relapse less than 12 months after completion of first-line therapy (36% vs 68%, P< .001), and prior rituximab exposure in the frontline setting (34% vs 66%, P< 0.001). [118] The preliminary results of the CORAL study validate the predictive factor of the aaIPI at the time of relapse, as previously described, and stress again that rituximab chemotherapy in the frontline is selective for forms of DLBCL more difficult to control in the salvage setting.

Final results of this study are eagerly awaited to further define the optimal salvage regimen and the role of rituximab maintenance following HDC-ASCS in relapsed/refractory DLBCL.

In general, when selecting the optimal salvage regimen, consider regimens with higher response rates, especially higher complete response (CR rates), low hematological and nonhematological toxicity, and a lesser degree of stem cell damage to secure effective peripheral blood stem-cell collection (PBSC).


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