**2.4 Antibody drug conjugates (ADCs)**

BCMA, is a and member of the tumor necrosis factor receptors (TNFR) superfamily [53, 54]. BCMA is primarily expressed in late-stage B-lineage cells, normal and malignant plasma cells, and B-lymphocytes, with very low expression on nonhematologic cells [55]. BCMA has two main ligands: a proliferation-inducing ligand (APRIL) and B-cell activating factor (BAFF) [56–58]. Following binding of APRIL and BAFF, BCMA expression is selectively upregulated during malignant transformation of plasma cells, playing a critical role in survival, drug resistance, and tumor cell growth through activation of intracellular signal transduction pathways such as STAT3, phosphoinositide 3-kinase (PI3K), AKT, NFB and MAPK [59–63]. As demonstrated in BCMA knock-down mouse models, BCMA is not required for normal B-cell differentiation and homeostasis [64]. The shedding of BCMA from the cell surface is mediated by γ-secretase and results in a soluble form (soluble BCMA, sBCMA). Higher sBCMA levels have been associated with inferior clinical outcomes. In preclinical models, inhibition of BCMA, with specific antibodies, showed significant anti-myeloma activity. The aforementioned facts make BCMA an ideal therapeutic target for the treatment of Multiple Myeloma and provide the rationale for the development of anti-BCMA monoclonal antibodies.

GSK2857916 (Belantamab Mafodotin) is the first anti-BCMA ADC that has been investigated in clinical trials. This afucosylated, humanized, IgG1 monoclonal antibody is conjugated to monomethyl auristatin F (MMAF), an inhibitor of tubulin polymerization, through a protease-resistant maleimidocaproyl linker. Following binding to the plasma cell surface, GSK2857916 is internalized and the active cytotoxic drug (cys-mcMMAF) is released following enzymatic cleavage leading to cell death. Mechanisms of action include NK-cell mediated ADCC and ADCP [65].

DREAMM 1 (NCT02064387) is a first in human phase I, open-label study, which evaluated the administration of GSK2857916 in patients with RRMM and other hematologic malignancies expressing BCMA in terms of efficacy and safety. Dose escalation cohort (part I) included solely patients with MM who have failed previous treatment regimens, including stem cell transplant (if eligible) IMiDs, PIs, and alkylators, while the dose-expansion cohort (part2) included both patients with MM and relapsed follicular lymphoma or diffuse large B-cell lymphoma. Regarding MM patients in the expansion cohort, 57% had five or more prior lines of therapy; 89% were double (PI and IMiD) and 34% triple (PI, IMiD, and daratumumab) refractory. GSK2857916 was administered intravenously every three weeks as a 1 hr. infusion in 38 patients at different dose levels (0.03–4.6 mg/kg). Primary endpoints were safety, determination of maximum tolerated dose (MTD), and recommended phase 2 dose. Secondary objectives were the determination of pharmacodynamics and pharmacokinetics parameters, anti-drug antibodies, and clinical activity. In dose-expansion, patients received the selected recommended phase 2 dose of 3.4 mg/kg. Overall, 73 patients were recruited, thirty-eight in dose escalation and thirty-five in the dose-expansion cohort. Notably, BCMA expression was not included in the eligibility criteria of study [66].

Updated results of this study, after an extended median follow-up of 12.5 months, demonstrate that was effective in this heavily pretreated group of patients [67]. Achievement of response occurred early during the study after the first or second infusion. Interestingly, dose reduction did not affect the depth and duration of response. 21/65 patients in the dose-expansion part achieve partial or better response, including 2PRs, 14VGPRs, 3CRs, and two sCRs. 18/32 (56.3%)

patients who were double refractory (IMiDs and PIs) achieved response to treatment. For double refractory patients (IMiDs and PIs), with prior Daratumumab exposure, OR was 38.5%. The median PFS and DOR were 12 and 14.3 months, respectively. Among double refractory patients, the median PFS was 7.9 months. For patients with and without prior Daratumumab exposure, median PFS was 6.8 and 15.7 months, respectively. For double refractory patients with prior Daratumumab exposure, median PFS was 6.2 months [67].

The most frequent AEs were fatigue, nausea, chills, anemia, pyrexia, hypercalcemia, thrombocytopenia, and dry eye, while the most common grade 3 or 4 toxicities included neutropenia, anemia, and thrombocytopenia. Infusion-related reactions (IRRs) (Grade 1 or 2) were reported in 7 patients across all dose levels, and all of them occurred during the first dose. Of note, there were no dose-limiting toxicities (DLT) and no MTD identified in the dose-escalation phase. Ocular toxicity, including blurred vision, foreign body sensation, and photophobia, were common presented in 53% of patients in part 1 and in 63% in part 2. Most common findings during eye examination under a slim lamp included keratitis and corneal microcystic changes. All AEs were reversible. The median time to onset was 23 days (range 1–84). Management included dose reductions and/or delays, artificial tears, and steroid eye drops. The median time to resolution was 30 days (range 5–224). Even though the exact pathophysiologic mechanism of keratopathy is unknown, it may be attributed to the uptake of the payload (MMAF) in the basal epithelial layer of the cornea 2938270. Ocular toxicity resulted in two treatment discontinuations in part 1 and no discontinuations in part 2 of the study. The main reasons for treatment discontinuation were disease progression (n = 15) and AEs (n = 2). Based on these promising results, FDA granted GSK2857916 a breakthrough therapy designation for the treatment of RRMM patients who had receive three prior lines of treatment, including an anti-CD38 antibody, and were refractory to both an IMiD and a PI [68].

Following the encouraging results of DREAMM-1 study, the subsequent DREAMM-2 trial (NCT03525678) further explored the safety and activity of Belantamab mafodotin (GSK2857916) in the RR setting. Patients were refractory to PI, IMiD and an anti-CD38 mAb alone or in combination and randomized 1:1 to receive 2.5 mg/kg (n = 97) or 3.4 mg/kg (n = 99) Belantamab Mafodotin iv, every three weeks until disease progression or unacceptable toxicity. Regarding refractoriness to previous lines of treatment, 76% and 75% were refractory to bortezomib, 65% and 58% to Carfilzomib, 90% and 89% to Lenalidomide, 87% and 78% to Pomalidomide and 100% and 92% to Daratumumab in the 2.5 and 3.4 mg/kg dose arms, respectively. Patients had receive a median of 6 (range 3–21) and 7(range 3–21) prior lines of treatment, respectively [69].

Overall response rate (ORR) was the primary objective of the study. After a median follow up of 6.5 months (6.3 in the 2.5 mg cohort and 6.9 in the 3.4 mg cohort), median PFS was 2.9(95% CI: 2.1–3.7) and 4.9(95% CI: 2.3–6.2) months in the two groups while the ORR was 31% (30/97 97.5% CI 20.8–42.6) and 34% (34/99CI 23.9–46) respectively 31859245. At this time point, OS data were not mature. Updated analysis of this trial, with a median, follow up of 9 months, demonstrated a median PFS of 2.8 and 3.9 months in the two cohorts with one year OS probability of 53% 21/48 and similar ORR among the group of patients with 3–6 (34%) and seven or more (30%) prior lines of therapy [69]. Two post hoc analyses demonstrate the efficacy of Belantamab mafodotin in the subgroups of patients with high-risk cytogenetics and impaired renal function (EGFR 30 ml/min) [70, 71].

Regarding AEs, this study confirmed the frequent occurrence of corneal events. 72% of patients developed keratopathy of any grade, while 31% developed

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*Antibody Therapies for Multiple Myeloma DOI: http://dx.doi.org/10.5772/intechopen.98656*

No new safety signals have emerged.

in the RRMM setting.

eagerly awaited.

cytic lymphohistiocytosis in the 3.4 mg/kg cohort.

keratopathy grade 3–4. Keratopathy was attributed to the MMAF payload and was reversible after temporary discontinuation of the drug. Other frequent adverse events grade 3–4 were anemia (21%) and thrombocytopenia (22%). Infusion-related reactions (IRRs) were reported in 21% and 16% in the two treatment arms and were mostly grade 1 or 2. Serious AEs occurred in 40% and 47% in the 2.5 mg/kg and 3.4 mg/kg cohorts respectively. Two reported cases lead to death, potentially connected to study drug. One case of sepsis in the 2.5 mg/kg and one of haemophago-

Currently, the role of Belantamab Mafodotin (GSK2857916) is being evaluated

Three-phase III studies are currently ongoing, evaluating the safety and efficacy

MEDI2228 is another antibody-drug conjugate (ADC) composed of fully human

Bispecific T-cell engagers (BiTEs) are monoclonal antibodies with two separate antigen recognition domains. One with a high affinity to an antigen in the surface of tumor cell and another targeting CD-3 in the surface of T-cells. Binding to those two distinct epitopes leads to the formation of an immunologic synapse. Binding to the CD3e epitope augments the t-cell recruitment and activation, leading to cell death. In MM, the majority of BiTEs targeting BCMA in the surface of plasma cells. AMG-420, formerly known as BI 836909, is the first BiTE demonstrating clinical activity. It is comprised of two single-chain variable fragments (scFvs), one targeting BCMA and one targeting CD3. AMG-420 is the compound with the

of belantamab mafodotin in combination with Pomalidomide (NCT04162210; DREAMM-3) daratumumab plus bortezomib (NCT04246047; DREAMM-7) or Pomalidomide plus Bortezomib (NCT04484623: DREAMM-8). The results are

monoclonal antibody, conjugated to a dimeric cross-linking pyrrolobenzodiazepine (PBD) dimer (tesirine) via a protease-cleavable dipeptide (valine-alanine) linker8/42 MEDI2228 has shown potent antitumor activity in preclinical models, including cell lines resistant to Lenalidomide. Based on these reports, a phase I open-label, dose-escalation, and expansion first in-human study (NCT03489525) evaluated safety, clinical activity, and pharmacokinetics of MEDI2228 in patients with RRMM. All patients had progressive disease after treatment with an IMiD, a PI, and a monoclonal antibody. In the dose-escalation part of the study, MEDI2228 was administered iv every three weeks in five sequentially ascending dose levels (0.0125, 0.025, 0.05, 0.1, and 0.2 mg/kg). DLTS lead to dose de-escalation from 0.2 mg/kg to 0.14 mg/kg. Primary endpoints included safety and tolerability. 0.14 mg/kg Q3W was determined as the maximum tolerated dose (MTD). In the 0.14 mg/kg cohort 53.7% experienced photophobia and 19.5% eye dryness. There were no incidents of visual acuity loss or keratopathy in the 0.14 mg/kg cohort. Other treatment-related AEs included thrombocytopenia (31.7%) rash (29.3%), increased gamma-glutamyltransferase (24.4%) and pleural effusion (19.5%). In the 0.14 mg/kg cohort, ORR was 61.0% (95% [CI]: 44.5%, 75.8%), including 10 (24.4%) VGPRs and 15 (36.6%) PR. These data suggest that MEDI2228 is clinically

efficient in this heavily pretreated group of patients [72].

**2.5 Bispecific antibodies**

DREAMM-6 (NCT03544281) is an ongoing Phase I/II, a two-part study of GSK2857916 in combination with lenalidomide/dexamethasone (Arm A) or BorDex (Arm B) in patients with RRMM who had received ≥one prior therapy. Refractory to Bortezomib patients were not excluded. Preliminary results from Arm B, presented in the last ASH meeting, have shown a high ORR of 78% (95% CI 52.4–93.6).

#### *Antibody Therapies for Multiple Myeloma DOI: http://dx.doi.org/10.5772/intechopen.98656*

keratopathy grade 3–4. Keratopathy was attributed to the MMAF payload and was reversible after temporary discontinuation of the drug. Other frequent adverse events grade 3–4 were anemia (21%) and thrombocytopenia (22%). Infusion-related reactions (IRRs) were reported in 21% and 16% in the two treatment arms and were mostly grade 1 or 2. Serious AEs occurred in 40% and 47% in the 2.5 mg/kg and 3.4 mg/kg cohorts respectively. Two reported cases lead to death, potentially connected to study drug. One case of sepsis in the 2.5 mg/kg and one of haemophagocytic lymphohistiocytosis in the 3.4 mg/kg cohort.

Currently, the role of Belantamab Mafodotin (GSK2857916) is being evaluated in the RRMM setting.

DREAMM-6 (NCT03544281) is an ongoing Phase I/II, a two-part study of GSK2857916 in combination with lenalidomide/dexamethasone (Arm A) or BorDex (Arm B) in patients with RRMM who had received ≥one prior therapy. Refractory to Bortezomib patients were not excluded. Preliminary results from Arm B, presented in the last ASH meeting, have shown a high ORR of 78% (95% CI 52.4–93.6). No new safety signals have emerged.

Three-phase III studies are currently ongoing, evaluating the safety and efficacy of belantamab mafodotin in combination with Pomalidomide (NCT04162210; DREAMM-3) daratumumab plus bortezomib (NCT04246047; DREAMM-7) or Pomalidomide plus Bortezomib (NCT04484623: DREAMM-8). The results are eagerly awaited.

MEDI2228 is another antibody-drug conjugate (ADC) composed of fully human monoclonal antibody, conjugated to a dimeric cross-linking pyrrolobenzodiazepine (PBD) dimer (tesirine) via a protease-cleavable dipeptide (valine-alanine) linker8/42 MEDI2228 has shown potent antitumor activity in preclinical models, including cell lines resistant to Lenalidomide. Based on these reports, a phase I open-label, dose-escalation, and expansion first in-human study (NCT03489525) evaluated safety, clinical activity, and pharmacokinetics of MEDI2228 in patients with RRMM. All patients had progressive disease after treatment with an IMiD, a PI, and a monoclonal antibody. In the dose-escalation part of the study, MEDI2228 was administered iv every three weeks in five sequentially ascending dose levels (0.0125, 0.025, 0.05, 0.1, and 0.2 mg/kg). DLTS lead to dose de-escalation from 0.2 mg/kg to 0.14 mg/kg. Primary endpoints included safety and tolerability. 0.14 mg/kg Q3W was determined as the maximum tolerated dose (MTD). In the 0.14 mg/kg cohort 53.7% experienced photophobia and 19.5% eye dryness. There were no incidents of visual acuity loss or keratopathy in the 0.14 mg/kg cohort. Other treatment-related AEs included thrombocytopenia (31.7%) rash (29.3%), increased gamma-glutamyltransferase (24.4%) and pleural effusion (19.5%). In the 0.14 mg/kg cohort, ORR was 61.0% (95% [CI]: 44.5%, 75.8%), including 10 (24.4%) VGPRs and 15 (36.6%) PR. These data suggest that MEDI2228 is clinically efficient in this heavily pretreated group of patients [72].

#### **2.5 Bispecific antibodies**

Bispecific T-cell engagers (BiTEs) are monoclonal antibodies with two separate antigen recognition domains. One with a high affinity to an antigen in the surface of tumor cell and another targeting CD-3 in the surface of T-cells. Binding to those two distinct epitopes leads to the formation of an immunologic synapse. Binding to the CD3e epitope augments the t-cell recruitment and activation, leading to cell death. In MM, the majority of BiTEs targeting BCMA in the surface of plasma cells.

AMG-420, formerly known as BI 836909, is the first BiTE demonstrating clinical activity. It is comprised of two single-chain variable fragments (scFvs), one targeting BCMA and one targeting CD3. AMG-420 is the compound with the most available data to date. In a first in human dose-escalation study, AMG420 was administered in 42 patients with RRMM (NCT02514239). Eligible patients had progressed after a minimum of 2 prior lines of treatment, including a PI and an IMiD 31895611. The median number of prior lines of therapy was 4 (range 2–13). 31% of patients were double refractory to IMiDs and PIs, and 21% were daratumumab refractory. AMG420 was administered at different dose levels, 0.2-800 μg/d, through a continuous iv infusion for four weeks in 6-week cycles due to its low molecular weight and short half-life. Patients received treatment for up to 10 cycles Monitoring of toxicities required hospitalization at the beginning of cycles one (4 days) and two (1 day) [73].

There were two deaths reported from adverse events: One patient in the 50 μg/d cohort died after the first cycle due to respiratory distress syndrome caused by concurrent influenza and aspergillosis, and one from hepatic failure from adenovirus. None of these incidents were considered related to treatment. There were no grade 3 or greater CNS toxicities reported. At the 800 μg/d dose level, two-thirds of the patients experienced DLTs. One patient had gr 3 CRS and one gr 3 peripheral polyneuropathy, which included progressive dysfunction of the peripheral motor and sensory nerves. Following the interruption of the study drug, both toxicities resolved. No DLTs were observed up to the level of 400 μg/d. In the most recent follow-up of the study, 40 patients discontinued treatment. Twenty-five due to disease progression, seven due to AEs, four died, three completed treatment (10 cycles), and 1 withdraw consent [73]. ORR was 31% (13/42patients). At the MTD of 400 μg/d, the response rate was 70% (7/10). In the 400 μg/d group, five patients achieved MRD negativity, one achieved PR, and one VGPR.

As mentioned, because of its low molecular weight and short half-life, AMG420 was administered through a continuous iv infusion for four weeks in 6-week cycles due to its low molecular weight and short half-life. AMG 701, a BiTE with an extended half-life allowing once-weekly subcutaneous administration, was developed and is currently under investigation (NCT03287908).

PF-06863135 (PF-3135) is a humanized Ig-like Bispecific antibody targeting both BCMA and CD3. PF-06863135 has been administered intravenously at 0.1–50 μg/kg weekly in patients with RRMM. Preliminary results demonstrate antimyeloma activity. The maximum tolerated dose was not reached [74]. In order to reduce the maximum concentration (Cmax) of the drug, which was possibly associated with inflammatory response and cytokine release syndrome (CRS), subcutaneous administration of the drug was tested. Preliminary results were reported in the last ASH meeting [75]. 2 6/8(75%) patients achieved a response at the two highest dose levels evaluated. The sc administration modulates Cmax. This could allow the administration of higher doses without increased incidence of CRS. The trial is ongoing.

## **3. Immune checkpoint inhibitors**

The programmed death-1 (PD-1) receptor is a type-1 transmembrane glycoprotein, expressed on antigen-activated B-cells, T-cells, and NK-cells. The binding of PD-1 ligands (PD-L1 and PD-L2) on PD-1 receptor results in downregulation of immune functions mediated by T-cells such as cytokine production, t-cell proliferation, and cytotoxicity [76]. The overexpression of PD-L1 and PD-L2 is a well recognizable mechanism of immune evasion. Preclinical data from MM patients have shown an increased expression of PD-L1 and PD-1 on malignant plasma cells and T and NK cells respectively [77, 78]. The deciphering of this particular mechanism of action has lead to the development of immune checkpoint inhibitors that

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*Antibody Therapies for Multiple Myeloma DOI: http://dx.doi.org/10.5772/intechopen.98656*

A Study of Daratumumab Plus Lenalidomide Versus Lenalidomide Alone as Maintenance Treatment in Participants With Newly Diagnosed Multiple Myeloma Who Are Minimal Residual Disease Positive After Frontline Autologous Stem Cell Transplant

Study of Melphalan Flufenamide (Melflufen) in Combination With Daratumumab in Relapsed Refractory Multiple Myeloma (LIGHTHOUSE)

Daratumumab, VELCADE (Bortezomib), Lenalidomide and Dexamethasone Compared to VELCADE, Lenalidomide and Dexamethasone in Subjects With Previously Untreated Multiple

Isatuximab Bortezomib, Lenalidomide and Dexamethasone Combination in NDMM Patients Not

Isa-KRd vs. KRd in Newly Diagnosed Multiple Myeloma Patients Eligible for Autologous Stem Cell

Study of Single Agent Belantamab Mafodotin Versus Pomalidomide Plus Low-dose Dexamethasone (Pom/ Dex) in Participants With Relapsed/Refractory

Study Evaluating Safety, Tolerability and Clinical Activity of GSK2857916 in Combination With Pembrolizumab in Subjects With Relapsed/Refractory

Platform Study of Belantamab Mafodotin as Monotherapy and in Combination With Anti-cancer Treatments in Participants With Relapsed/Refractory Multiple Myeloma (RRMM) (DREAMM 5)

To Evaluate Safety, Tolerability, and Clinical Activity of the Antibody-drug Conjugate, GSK2857916 Administered in Combination With Lenalidomide Plus Dexamethasone (Arm A), or in Combination With Bortezomib Plus Dexamethasone (Arm B) in Participants With Relapsed/Refractory Multiple

Evaluation of Efficacy and Safety of Belantamab Mafodotin, Bortezomib and Dexamethasone Versus Daratumumab, Bortezomib and Dexamethasone in Participants With Relapsed/Refractory Multiple

Belantamab Mafodotin Plus Pomalidomide and Dexamethasone (Pd) Versus Bortezomib Plus Pd in Relapsed/Refractory Multiple Myeloma

Study of Belantamab Mafodotin Plus Standard of Care (SoC) in Newly Diagnosed Multiple Myeloma

Eligible for Transplant (IMROZ)

ANTIBODY-DRUG CONJUGATES

Multiple Myeloma (DREAMM-3)

Multiple Myeloma (DREAMM-4)

Myeloma (DREAMM-6)

Myeloma (DREAMM-7)

(DREAMM-8)

(DREAMM-9)

DARATUMUMAB

(AURIGA)

Myeloma (PERSEUS)

Transplantation (IsKia)

ISATUXIMAB

**Description Phase NCT number Population**

3 NCT03901963 NDMM

3 NCT04649060 RRMM

3 NCT03710603 NDMM

3 NCT03319667 NDMM

3 NCT04483739 NDMM

3 NCT04162210 RRMM

1/2 NCT03848845 RRMM

1/2 NCT04126200 RRMM

1/2 NCT03544281 RRMM

3 NCT04246047 RRMM

3 NCT04484623 RRMM

1 NCT04091126 NDMM



#### **Table 1.**

*Ongoing clinical trials.*

block receptors (PD-1) and ligands (PD-L1 and PD-L2), resulting in the recovery of immune response.

Pembrolizumab is a humanized IgG4 monoclonal antibody with high specificity against PD-1 receptors. Pembrolizumab was evaluated in combination with Lenalidomide and low dose dexamethasone in a phase I dose-escalation study (KEYNOTE-023 trial NCT02036502). Sixty-six patients with RRMM were recruited. Pembrolizumab was treatment-related AEs. Grade 3 AEs (mainly cytopenias fatigue and diarrhea) occurred in 37 (59,7%) patients. ORR OS and median PFS were 44%, not reached, and 7.2 months respectively [79, 80]. Pembrolizumab has also been evaluated in combination with Pomalidomide and dexamethasone in another phase II study (NCT02289222). Forty-eight patients with RRMM were recruited. Patients had received 2–5 (median 3) prior lines of treatment. 73% were refractory to both IMIDs and PIs. ORR was 60%. The percentage of SCR and CR, VGPR, and PR were 8%, 19%, and 33%, respectively. After a median follow-up of 15.6 months, OS and PFS were not reached and 17.4 months, respectively. (40%) [81].

Based on these results, two-phase three trials were designed to evaluate the combination of Pembrolizumab dexamethasone with Lenalidomide (KEYNOTE-185 NCT02579863) or Pomalidomide (KEYNOTE-183 NCT02576977) in ND and RR setting respectively. Interim analysis of both studies showed excessive administered for a median of 7 cycles (range 1–67). Overall, 95% of patients experienced unanticipated deaths attributed to the combination of Pembrolizumab Dexamethasone with Lenalidomide or Pomalidomide. These results showed that the risk profile of these novel combinations was unfavorable, and both trials were terminated early [82, 83].

Nivolumab is a fully human IgG4 Moab targeting PD-1 receptors. Investigation of Nivolumab with IMiDS has been placed on clinical hold after reviewing data

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**Author details**

Nikolaos Kanellias\*, Maria Gavriatopoulou and Evangelos Terpos

National and Kapodistrian University of Athens, Athens, Greece

\*Address all correspondence to: nick.kanellias@gmail.com

provided the original work is properly cited.

Department of Clinical Therapeutics, Medical School, Alexandra General Hospital,

© 2021 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/ by/3.0), which permits unrestricted use, distribution, and reproduction in any medium,

*Antibody Therapies for Multiple Myeloma DOI: http://dx.doi.org/10.5772/intechopen.98656*

**4. Conclusion**

regarding Pembrolizumab. Nivolumab is currently under investigation in combination with daratumumab (NCT03184194), Elotuzumab (NCT02612779), Pomalidomide (NCT02726581), and Carfilzomib (NCT03605719) in phase 2 trials. In **Table 1**, we present selected clinical trials conducted with monoclonal

Despite therapeutic improvements Multiple Myeloma remain an incurable disease. The treatment of patients with RR remains a challenging issue. Antibody therapy has significantly enhanced the armamentarium of therapeutic options. Further research should focus on tailoring the combination regimens based on disease and patient characteristics in order to optimize the efficacy and safety.

antibodies in the newly diagnosed and relapsed refractory setting.

#### *Antibody Therapies for Multiple Myeloma DOI: http://dx.doi.org/10.5772/intechopen.98656*

regarding Pembrolizumab. Nivolumab is currently under investigation in combination with daratumumab (NCT03184194), Elotuzumab (NCT02612779), Pomalidomide (NCT02726581), and Carfilzomib (NCT03605719) in phase 2 trials.

In **Table 1**, we present selected clinical trials conducted with monoclonal antibodies in the newly diagnosed and relapsed refractory setting.
