**3.2 Daratumumab in relapsed/refractory multiple myeloma in combination therapy: after or before allogenic hematopoietic cell-transplantation for young patients?**

Despite improvements in the MM outcome and in the depth and response duration following subsequent lines of therapy, MM remains an incurable disease. It is reasonable to consider allogenic (allo) hematopoietic cell transplantation (HCT) as a treatment strategy for young patients with high-risk disease and an available

**73**

*The Modern Age of Monoclonal Antibodies: The Revolution of Daratumumab*

donor. Allo-HCT is potentially effective by virtue of a graft-versus-myeloma (GvM) effect but currently, there is little available data regarding this treatment [22]. Given the action of daratumumab on the microenvironment, it could be used both to control the graft-versus-host disease and to improve the GvM effect. In the review by Nikolaenko et al., 34 patients treated with daratumumab after aploidentical HCT were evaluated [23]. The ORR after the treatment with the monoclonal antibody was 41%, only five cases of acute GVHD were reported and no cases of chronic GVHD, showing the efficacy of this strategy on a population of high-risk heavily pretreated patients. Based on this little data, we may speculate that the modification of microenvironment induced by daratumumab could be used to "plow the land" for the transplant. To our knowledge, none is known about the use of anti-CD38 as a bridge to the transplant. We recently reported the case of a young patients with relapsed myeloma after the standard induction therapy and a tandem ASCT who underwent 11 cycles of rescue therapy with daratumumab in combination with lenalidomide and dexamethasone, followed by haploidentical transplant. Thanks to this treatment, he achieved a partial response and is now on consolidation with

**4. Daratumumab in untreated newly diagnosed multiple myeloma**

More recently, the use of daratumumab has been also explored in the setting of newly diagnosed multiple myeloma (NDMM) patients, showing encouraging results both in the population of transplant eligible patients and in that of transplant ineligible patients. The first results about daratumumab in NDMM patients proceed from a phase 1b study evaluating tolerability and safety of this monoclonal antibody in combination with myeloma backbone regimens: bortezomib-dexamethasone (VD), bortezomib-thalidomide-dexamethasone (VTD), bortezomibmelphalan-dexamethasone (VMP), pomalidomide-dexamethasone (PD) [25]. NDMM patients were included in all the arms except the PD one: in the VD and VTD arms the patients were enrolled irrespective of the transplant eligibility, while all patients in the VMP arm were transplant ineligible. In all the four arms, daratu-

**4.1 Daratumumab in untreated newly diagnosed multiple myeloma: transplant** 

ALCYONE and MAIA are the two main trials which evaluated the efficacy of adding daratumumab in the standard treatment of untreated patients with multiple myeloma ineligible to transplant. ALCYONE enrolled 706 naive patients randomized to receive VMP alone or with daratumumab [26]. Each cycle had a duration of 42 days. In the control group, all the patients received up to nine cycles of subcutaneous bortezomib, administered at the dosage of 1.3 mg per square meter of body-surface area (twice weekly on weeks 1, 2, 4, and 5 of cycle 1 and once weekly on weeks 1, 2, 4, and 5 of cycles 2 through 9), oral melphalan (9 mg per square meter, once daily on days 1 through 4 of each cycle), and oral prednisone (60 mg per square meter, once daily on days 1 through 4 of each cycle). In the experimental group, intravenous daratumumab at the usual dose of 16 mg/kg was administered with oral or intravenous dexamethasone at a dose of 20 mg once weekly in cycle 1, every 3 weeks in cycles 2 through 9, and every 4 weeks thereafter until disease progression or toxicity. Dexamethasone at a dose of 20 mg was substituted for prednisone on day 1 of each cycle. At 12 months, the PFS was 86.7% in the daratumumab group *vs* 76.0% in the control group. At the clinical data cut-off,

*DOI: http://dx.doi.org/10.5772/intechopen.95406*

Daratumumab-Rd regimen [24].

mumab was well tolerated and safe (**Table 1b**).

**ineligible patients**

#### *The Modern Age of Monoclonal Antibodies: The Revolution of Daratumumab DOI: http://dx.doi.org/10.5772/intechopen.95406*

donor. Allo-HCT is potentially effective by virtue of a graft-versus-myeloma (GvM) effect but currently, there is little available data regarding this treatment [22]. Given the action of daratumumab on the microenvironment, it could be used both to control the graft-versus-host disease and to improve the GvM effect. In the review by Nikolaenko et al., 34 patients treated with daratumumab after aploidentical HCT were evaluated [23]. The ORR after the treatment with the monoclonal antibody was 41%, only five cases of acute GVHD were reported and no cases of chronic GVHD, showing the efficacy of this strategy on a population of high-risk heavily pretreated patients. Based on this little data, we may speculate that the modification of microenvironment induced by daratumumab could be used to "plow the land" for the transplant. To our knowledge, none is known about the use of anti-CD38 as a bridge to the transplant. We recently reported the case of a young patients with relapsed myeloma after the standard induction therapy and a tandem ASCT who underwent 11 cycles of rescue therapy with daratumumab in combination with lenalidomide and dexamethasone, followed by haploidentical transplant. Thanks to this treatment, he achieved a partial response and is now on consolidation with Daratumumab-Rd regimen [24].
