New drugs and allogeneic hematopoietic stem cell transplantation for hematological malignancies: do they have a role in bridging, consolidating or conditioning transplantation treatment?

ABSTRACT

Introduction: Novel targeted therapies and monoclonal antibodies can be combined with allogeneic stem cell transplantation (allo-SCT) at different time-points: 1) before the transplant to reduce tumour burden, 2) as part of the conditioning in place of or in addition to conventional agents 3) after the transplant to allow long-term disease control.

Areas covered: This review focuses on the current integration of new drugs with allo-SCT for the treatment of major hematological malignancies for which allo-SCT has been a widely-adopted therapy.

Expert opinion: After having been used as single agent salvage treatments in relapsed patients after allo-SCT or in combination with donor lymphocyte infusions, many new drugs have also been safely employed before allo-SCT as a bridge to transplantation or after it as planned consolidation/maintenance. This era of new drugs has opened new important opportunities to ‘smartly’ combine ‘targeted drugs and cell therapies’ in new treatment paradigms that may lead to higher cure rates or longer disease control in patients with hematological malignancies

KEYWORDS:

• Allogeneic stem cell transplantation
• graft-versus-tumor
• monoclonal antibodies
• new drugs
• targeted therapy

Article highlights

• Targeted therapies can be integrated with allogeneic stem cell transplantation to treat patients with hematological malignancies.

• Hypomethylating agents can be employed as ‘bridge to transplant’ and as consolidation/maintenance after the procedure in patients with high risk myelodisplastic disease and acute myeloid leukemia.

• The monoclonal antibodies blinatumumab and inotuzumab can be an appropriate treatment to eradicate minimal residual disease in Ph negative acute lymphoblastic leukemia before transplant.

• Tyrosin kynase inhibitors have almost replaced allogeneic transplantation in chronic myeloid leukemia, but they are still used before and after allogeneic stem cell transplantation in high risk Ph positive acute lymphoblastic leukemia to reach negative molecular minimal residual disease.

• Allogeneic transplant is still a salvage option for selected young patients with lymphoma and multiple myeloma, who have reached at least a partial response after treatment with new drugs, including brentuximab, anti-PD-1 monoclonal antibodies, immuno-modulatory agents and proteosoma inhibitors.

• Some targeted drugs, such as ruxolitinib and bortezomib, have a promising role in the prophylaxis and treatment of graft-versus-host-disease due to their potent immuno-modulatory activity.

This box summarizes key points contained in the article.

Acknowledgments

The authors would like to thank the Steering Committee and the Clinical Trials Office of Gruppo Italiano Trapianti di Midollo (GITMO), Barbara Bruno and Sonia Mammoliti for excellent secretarial support.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Additional information

Funding

This manuscript has not been funded.