A Phase II Study of Daratumumab in Combination with Bortezomib and Dexamethasone in Patients with Multiple Myeloma Who Received One Prior Line of Therapy (KMM1906)

Kwai Han Yoo; Sang Eun Yoon; Ka-Won Kang; Jun Ho Yi; Min Kyoung Kim; Hyo Jung Kim; Sung-Hyun Kim; Joon Seong Park; Sung-Hoon Jung; Je-Jung Lee; Chang-Ki Min; Jae Hoon Lee; Duck Cho; Kihyun Kim

doi:10.4143/crt.2025.426

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Original Article A Phase II Study of Daratumumab in Combination with Bortezomib and Dexamethasone in Patients with Multiple Myeloma Who Received One Prior Line of Therapy (KMM1906): Kwai Han Yoo¹, Sang Eun Yoon², Ka-Won Kang³, Jun Ho Yi⁴, Min Kyoung Kim⁵, Hyo Jung Kim⁶, Sung-Hyun Kim⁷, Joon Seong Park⁸, Sung-Hoon Jung⁹, Je-Jung Lee⁹, Chang-Ki Min¹⁰, Jae Hoon Lee¹, Duck Cho¹¹, Kihyun Kim²; DOI: https://doi.org/10.4143/crt.2025.426
Published online: June 30, 2025

¹Division of Hematology, Department of Internal Medicine, Gachon University Gil Medical Center, Gachon University College of Medicine, Incheon, Korea

²Division of Hematology and Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea

³Division of Hematology and Oncology, Department of Internal Medicine, Korea University Anam Hospital, Korea University College of Medicine, Seoul, Korea

⁴Department of Internal Medicine, Chung-Ang University Hospital, Seoul, Korea

⁵Department of Internal Medicine, Yeungnam University College of Medicine, Daegu, Korea

⁶Division of Hematology/Oncology, Department of Internal Medicine, Hallym University Sacred Heart Hospital, Hallym University College of Medicine, Anyang, Korea

⁷Department of Internal Medicine, Dong-A University Medical Center, Dong-A University College of Medicine, Busan, Korea

⁸Department of Hematology-Oncology, Ajou University School of Medicine, Suwon, Korea

⁹Department of Hematology-Oncology, Chonnam National University Hwasun Hospital and Chonnam National University Medical School, Hwasun, Korea

¹⁰Department of Internal Medicine, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea

¹¹Department of Laboratory Medicine and Genetics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea

Correspondence: Kihyun Kim, Division of Hematology and Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-ro, Gangnam-gu, Seoul 06351, Korea
Tel: 82-2-3410-1766 E-mail: kihyunk@skku.edu

• Received: April 18, 2025 • Accepted: June 27, 2025

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

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Abstract

Purpose
Daratumumab combined with bortezomib and dexamethasone (DVd) has been established as the standard treatment for relapsed/refractory multiple myeloma (MM) based on pivotal phase 3 trials. A subgroup analysis demonstrated enhanced efficacy in the second-line setting, although the fixed duration of bortezomib administration remained a limitation. Therefore, we conducted a phase II trial evaluating continuous bortezomib as maintenance in a DVd regimen for second-line treatment.
Materials and Methods
This phase II study (KCT0004352) enrolled patients with MM receiving second-line DVd therapy: daratumumab (16 mg/kg IV, weekly for cycles 1-3, every 3 weeks for cycles 4-8, every 4 weeks thereafter), bortezomib (1.3 mg/m² subcutaneously, twice weekly for cycles 1-8, biweekly thereafter), and dexamethasone (20 mg IV or orally on treatment days), as in the pivotal trial. After nine cycles, daratumumab and bortezomib were continued until progression or unacceptable toxicity. The primary endpoint was a ≥ very good partial response (VGPR). Secondary endpoints included progression-free survival (PFS), overall survival (OS), safety, and minimal residual disease (MRD) negativity assessed by EuroFlow-based next-generation flow in bone marrow.
Results
Between June 2020 and 2021, 26 patients (median age, 72 years) from 10 Korean centers were enrolled. All had one prior treatment line; 73% had prior bortezomib, and 69% had prior immunomodulators. At a median follow-up of 25.4 months, 65% discontinued due to progression, death, or withdrawal. VGPR or better was achieved in 65%, with 23% MRD-negative. Median PFS was 21.8 months; OS was not reached. The 24-month OS rate was 69.2%. Grade 3 adverse events included thrombocytopenia and lymphopenia; 31% had serious adverse events, and 65% required dose modifications.
Conclusion
Continuous DVd therapy showed promising efficacy and manageable toxicity as a second-line option.
Key words: Multiple myeloma, Salvage therapy, Daratumumab, Proteasome inhibitors, Residual neoplasm

Introduction

Multiple myeloma (MM) is characterized by the clonal growth of plasma cells in the bone marrow (BM), often resulting in end-organ damage such as lytic bone lesions, renal impairment, anemia, and hypercalcemia [1]. Its pathogenesis involves complex interactions between malignant plasma cells and the BM microenvironment, leading to progression and resistance to treatment [2]. Over the past two decades, the treatment for MM has significantly advanced, primarily due to novel therapeutic agents. Initial treatments typically combine chemotherapy, steroids, and new drugs like proteasome inhibitors (PIs) or immunomodulatory drugs (IMiDs), with autologous stem cell transplantation being an option for eligible patients [1,3,4]. Despite these advancements, MM is incurable, with many patients experiencing relapse. Managing relapsed MM requires considering factors such as the patient’s response to prior therapy, overall health, and comorbidities [5]. The emergence of new drugs like monoclonal antibodies and second-generation PIs has expanded treatment options for relapsed or refractory MM [6,7]. Combination therapies that utilize the synergistic effects of different drugs have shown promising results in improving progression-free survival (PFS) and overall survival (OS) [8].

In recent years, the survival rate for MM patients has dramatically improved, although relapse remains common, necessitating the ongoing development of new therapies. Daratumumab, a humanized IgGκ monoclonal antibody targeting CD38 highly expressed on myeloma cells, demonstrates both direct and indirect anti-tumor activities and immunomodulatory functions [9]. In relapsed or refractory MM, daratumumab as a monotherapy has improved overall response rates (ORR) and median survival [10]. The phase 3 studies CASTOR and POLLUX explored daratumumab in combination with PIs or IMiDs, revealing enhanced ORRs and PFS compared to standard bortezomib–dexamethasone or lenalidomide–dexamethasone treatments [11,12]. In the post-hoc subgroup analysis of the CASTOR trial, the efficacy was more prominent in the second, and there was criticism of the fixed duration of bortezomib treatment duration [13,14].

Hence, we conducted a phase II trial of daratumumab combined with bortezomib and dexamethasone (DVd) as second-line treatment and continuous treatment with bortezomib as a maintenance treatment.

Materials and Methods

1. Study design and procedures

This study is a phase II clinical trial of DVd therapy in patients with MM who had received one prior line of treatment (KCT0004352). All patients received daratumumab, bortezomib, and dexamethasone. Daratumumab at a dose of 16 mg/kg was administered intravenously once per week (days 1, 8, and 15) during cycles 1 to 3, once every 3 weeks (on day 1) during cycles 4 to 8, and once every 4 weeks thereafter until the patient withdrew consent, the disease progressed, or unacceptable adverse effects developed. Bortezomib was administered subcutaneously at a dose of 1.3 mg/m² on days 1, 4, 8, and 11 of cycles 1 to 8, and dexamethasone was administered orally or intravenously at a dose of 20 mg on days 1, 2, 4, 5, 8, 9, 11, and 12. From cycle nine onwards, bortezomib was administered on day 1 and day 15, and dexamethasone on days 1, 2, 15, and 16, every 4 weeks (S1 Fig.).

2. Participants and eligibility criteria

This study included patients aged 18 and over who had received at least one cycle of first-line treatment for MM and had disease progression (PD) confirmed according to the International Myeloma Working Group (IMWG) response criteria [15].

The inclusion criteria for relapsed or refractory MM are as follows: (1) monoclonal plasma cells ≥ 10% in the BM or a plasmacytoma confirmed by biopsy, and (2) patients with measurable MM fulfilling at least one of the following: serum M-protein ≥ 1.0 g/dL or urine M-protein ≥ 200 mg/24 hours, for IgA MM: serum M-protein ≥ 0.5 g/dL or urine M-protein ≥ 200 mg/24 hr, and for light chain myeloma: serum free light chains ≥ 10 mg/dL and an abnormal serum kappa/lambda free light chains ratio.

Patients who had received second-line or subsequent treatments for MM, those who had been treated with daratumumab or other anti-CD38 therapies, and patients who were refractory (PD during treatment or within 60 days after the last dose) or intolerant (grade ≥ 3 adverse events leading to drug discontinuation) to bortezomib were excluded from the study.

3. Assessment and statistical analysis

The primary endpoint was the rate of very good partial response (VGPR) or better. Among the enrolled patients, the percentage of those who achieve VGPR, complete response (CR), or stringent complete response (sCR) at any point from the start of DVd treatment until the end of the trial is defined based on the IMWG response criteria. An approximate 95% confidence interval (CI) is calculated.

Secondary endpoints include PFS, time to progression (TTP), ORR, OS, time to response (TTR), and duration of response (DOR). PFS is defined as the time from the initiation of DVd treatment to either PD or death from any cause. TTP is defined as the duration from the initiation of treatment to the confirmation of PD. OS is measured from the start of treatment until death from any cause. TTR represents the interval from treatment initiation to the first documented response (≥ partial response [PR]). DOR is defined as the duration from the initial documentation of response (≥ PR) until PD or death. The median PFS and its 95% CI are estimated using the Kaplan-Meier method. ORR is defined as the proportion of patients who achieve PR, VGPR, CR, or sCR from the start of treatment according to IMWG response criteria.

Safety evaluations include monitoring and assessing adverse events (AEs), drug-related reactions, toxicities, and clinical trial-related events, as per the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) ver. 5.0.

We estimated the response rate (VGPR or better) for DVd subjects as 76% (P1) compared with 42% (P0) for bortezomib and dexamethasone (Vd), based on the results of a pivotal study involving one prior line of treatment group [13]. To detect a difference in response rate (34%, P1-P0), the sample size was calculated using the two-sided binomial test. As a result, a sample of 23 subjects achieves 90% power at a two-sided significance level of 0.05. Assuming a 10% dropout rate, 26 subjects are required for the study.

4. Minimal residual disease monitoring

When participants reach serum/urine protein electrophoresis and immunofixation electrophoresis (IFE) negativity (achieving CR), BM aspiration and biopsy are performed, followed by minimal residual disease (MRD) testing with the BM aspirates. Considering the possibility of not achieving CR due to daratumumab (due to IFE positivity, interference of daratumumab) [16], in patients with VGPR, BM aspiration and biopsy, and MRD testing are performed twice, after 6 months and 12 months from the start of treatment.

According to the IMWG MRD criteria, MRD negativity is defined as the absence of detectable tumor cells in BM aspirates using next-generation flow (NGF) cytometry with a minimum sensitivity of 105. Testing must be conducted according to the EuroFlow standard operation procedure for MRD detection in MM, and the minimum sensitivity should be 105 or higher [17].

Results

1. Patients and treatment

From June 2020 to June 2021, 26 MM patients who received one prior line of therapy and disease progressed were enrolled at 10 centers in Korea—the demographic, disease, and clinical characteristics given in Table 1. The median age of all patients was 72 years (range, 47 to 85 years), and 69.3% were aged 65 years or older. Eight patients (30.8%) were male. At the time of initial diagnosis of MM, five patients (19.2%) were classified as International Staging System (ISS) I, 17 patients (65.4%) were in ISS II, and four patients (15.4%) were in ISS III. Upon relapse, five patients (19.2%) had high-risk cytogenetic abnormalities (t(4;14), t(14;16), or del17p), and six patients (23.1%) had extramedullary skeletal disease. The median time from the initial diagnosis of MM to enrollment in this study was 2.4 years. All patients were treated with one prior line, including VTD (bortezomib, thalidomide, and dexamethasone, n=11, 42.3%), VMP (bortezomib, melphalan, and prednisone, n=8, 30.7%), Rd (lenalidomide and dexamethasone, n=6, 23.1%), and CMP (cyclophosphamide, melphalan, and prednisone, n=1, 3.8%). Nineteen patients (73.1%) and 18 (69.2%) were exposed to bortezomib and IMiDs (thalidomide or lenalidomide), respectively, from previous treatment. Lenalidomide was exposed to seven patients, and six of them (23.1%) were refractory to lenalidomide.

2. Efficacy and MRD assessment

During the median follow-up period of 25.4 months, nine patients (34.6%) maintained treatment, and 17 patients (65.4%) discontinued the study due to PD (n=11), death from other causes (n=2), or withdrawal of consent (n=4). The reasons for withdrawal of consent were personal reasons unrelated to toxicity (n=2), transportation issues (n=1), and patient decision following recovery from AEs (n=1). Seventeen patients (65.4%) achieved ≥ VGPR (2 sCR, 8 CR, and 7 VGPR), and it did not meet the original hypothesis that expected 76% of patients to achieve VGPR or better. The CR rate was 38% (10/26) and the ORR was 85% (22/26) (Table 2).

Each patient’s treatment response and PFS were given in the swimmer plot (Fig. 1). The median PFS of all patients was 21.8 months (95% CI, 10.1 to 33.5), and OS was not reached (Fig. 2). The OS rate at 24 months was 69.2%. The median TTR was 1.4 months (95% CI, 0.8 to 2.2). The median DOR and TTP were 22.9 months (95% CI, 17.6 to 28.2) and 25.6 months (95% CI, 20.5 to 30.7), respectively. The MRD test was conducted on 13 patients, and 10 had a second MRD test. The MRD test was not performed in four VGPR patients due to patient refusal (n=2), logistical issues (n=1), and early progression (n=1). The MRD-negativity (10^-5) was confirmed in 45% (6/13) of patients at first BM aspiration and biopsy and in 23% of all patients in this trial. Among the patients who underwent MRD testing twice at an interval of more than six months, five were confirmed to have sustained MRD-negativity. One patient was positive in the first test but converted to negative in the second. In contrast, another showed the opposite pattern: negative in the first test but positive in the second. Patients who achieved MRD-negativity at least once (n=7) all remained on treatment without PD or death, demonstrating superior PFS (p=0.001) and OS (p=0.046) compared to those who did not (MRD-positive or worse) (Fig. 3).

3. Safety

Most patients (92.3%) experienced at least one AE during the study treatment. The most common AE of any grade was thrombocytopenia (n=24, 92.3%), and the most common AE ≥ grade 3 was lymphopenia (n=10, 38.5%). AEs occurring in at least 10% of patients are summarized in Table 3. Two coronavirus disease 2019 (COVID-19) infections and one grade 5 sepsis were noticed. During the study period, a total of 19 serious AEs occurred in eight patients (30.8%), with eight being related to infections, two instances of bone fractures, two COVID-19 infections, and one cardiac arrest. Although four cases (15.4%) of dose delays and 17 cases (65.4%) of dose reductions were observed, only three events were related to peripheral neuropathy, and these did not interfere with bortezomib maintenance beyond the ninth cycle.

Discussion

This Phase II clinical trial evaluated the efficacy of DVd combination therapy in patients with MM who had previously received one line of therapy and daratumumab with bortezomib maintenance. The study’s patient cohort, predominantly in the older age group with a median age of 72, reflects the demographic commonly affected by MM. The use of the DVd regimen in this population achieved a notable ORR of 85%, with 65% of patients achieving VGPR or better. Although our study did not achieve the initial hypothesis of ≥ 76% VGPR or better (based on the comparator group from the pivotal CASTOR study with DVd after one prior line of treatment), this result may be attributable to the higher median age of patients in our study compared to the comparator group (72 vs. 63 years), and the occurrence of early treatment discontinuation or mortality due to toxicities in our relatively small sample size. These results align with the outcomes observed in previous studies like CASTOR but extend our understanding to a population previously treated with only one line of therapy [18-21].

The median PFS of 21.8 months and 24-month OS rate of 69.2% are comparable to survival outcomes in the DVd arm of the CASTOR study [11,13]. Of 251 patients treated with DVd in the intention-to-treat (ITT) population in CASTOR, 47% had one prior line of treatment (n=122). In this subgroup (one prior line), the median PFS was 27 months, and OS was not reached at a median follow-up of 72.6 months [13,20]. Importantly, this trial underscores the relevance of MRD-negativity (10^-5) as a key outcome measure, with 15.1% in the DVd regimen versus 1.6% in Vd in the entire ITT population via next-generation sequencing using the clonoSEQ assay. [19]. Although our study utilized NGF cytometry based on EuroFlow, the fact that 23% (6/26) of MRD-negativity and superior survival outcomes were reported in patients who achieved MRD-negativity at least once (n=7) is also in line with this, providing evidence that MRD-negativity plays a crucial role as a predictor of prolonged survival in MM. However, our study was a phase II trial with a limited number of patients, making it difficult to draw definitive conclusions about the clinical significance of sustained MRD for more than six months.

From the perspective of safety profiles, most AEs were manageable. One of the main differences from the CASTOR study is that in this study, the Vd regimen (bortezomib and dexamethasone) was continued alongside daratumumab beyond nine cycles. As a result, there may be concerns regarding the long-term adverse effects of the Vd, such as peripheral neuropathy, hyperglycemia, and infections [22]. However, in this study, most of the dose reductions and delays of bortezomib due to neuropathy occurred in the early stages of treatment (within four cycles), and no events required new dose reductions or discontinuations of bortezomib after nine cycles. Additionally, no serious AEs related to hyperglycemia that impacted treatment were observed. Furthermore, severe infections such as grade 3 or higher pneumonia or sepsis mainly occurred in the early stages of treatment, and apart from wound infections after surgery for compression fractures, infection did not pose a serious problem in patients receiving long-term therapy beyond nine cycles with the DVd regimen. Hence, the addition of bortezomib was possible without the additional AEs.

Regarding hematologic AEs, there were few cases of thrombocytopenia or anemia requiring transfusion. However, grade 3 or higher lymphopenia was common and persisted long, increasing the risk of opportunistic infections, including COVID-19. In the long-term follow-up of the CASTOR study, the most common grade 3 or 4 treatment-emergent AEs with DVd were thrombocytopenia (46%), anemia (16%), neutropenia (14%), lymphopenia (10%), and pneumonia (11%) were also reported [20]. This highlights the importance of continuous monitoring and proactive management of treatment-related toxicities, such as infections, especially in older patients.

The study has several significant limitations, particularly the small sample size (n=26), which significantly restricts the generalizability and robustness of the findings. Additionally, the discontinuation rate of 65% due to PD or other factors highlights the necessity for ongoing and careful monitoring of treatment efficacy and patient tolerance. The single-arm design further complicates drawing definitive conclusions regarding the effectiveness of continuous DVd maintenance therapy. These limitations underscore the need for larger, controlled studies to validate our observations.

In conclusion, among patients with MM who received one prior line of therapy, the DVd regimen with maintenance strategy showed an acceptable clinical response and MRD-negativity with a manageable toxicity profile. Nonetheless, to solidify the efficacy of DVd maintenance therapy and to validate the impact of MRD, additional research involving a larger patient population is warranted.

Electronic Supplementary Material

Supplementary materials are available at Cancer Research and Treatment website (https://www.e-crt.org).

crt-2025-426_S1_Fig.pdf

NOTES

Ethical Statement

The study was conducted in strict compliance with the International Ethical Guidelines for Biomedical Research Involving Human Subjects, Good Clinical Practice (GCP) guidelines, and the Declaration of Helsinki. The study protocol and informed consent documents received approval from the institutional review boards (IRBs) at all participating institutions. Final approval was also obtained from the Korean Ministry of Food and Drug Safety (MFDS). Written informed consent was obtained from all participants before their involvement in the study. Additionally, the approved IRB protocol conducted all experimental procedures involving patient-derived specimens and molecular testing.

Author Contributions

Conceived and designed the analysis: Yoo KH, Kim K.

Collected the data: Yoo KH, Kang KW, Yi JH, Kim MK, Kim HJ, Kim SH, Park JS, Jung SH, Lee JJ, Min CK, Lee JH, Kim K.

Contributed data or analysis tools: Yoo KH, Cho D, Kim K.

Performed the analysis: Yoo KH, Cho D, Kim K.

Wrote the paper: Yoo KH, Kim K.

Conflict of Interest

This study was supported by research grant and investigational products from Janssen, Korea.

Funding

This work was supported by the Gachon University research fund of 2023 (GCU-202309110001).

Acknowledgments

This research was conducted under the auspices of the Korean Society of Hematology Multiple Myeloma Working Party (KMMWP). We thank the centers that participated in this study.

Fig. 1.

The CONSORT diagram of patient flow (A) and response and swimmer plot of progression-free survival (B). CR, complete response; MR, minimal response; MRD, minimal residual disease; PR, partial response; sCR, stringent complete response; SD, stable disease; VGPR, very good partial response.

Fig. 2.

Kaplan-Meier estimates of progression-free survival (A) and overall survival (B).

Fig. 3.

Kaplan-Meier estimates progression-free survival (A) and overall survival (B) by minimal residual disease (MRD) status.

Table 1.

Baseline characteristics

Characteristic	No. (%) (n=26)
Age (yr), median (range)	72 (47-85)
< 65	8 (30.7)
65-74	12 (46.2)
≥ 75	6 (23.1)
≤ 70 vs. ≥ 71	12 (46.2) vs. 14 (53.8)
Type of measurable disease
IgG	15 (57.7)
IgA	6 (23.1)
Detected in serum free light-chains only	5 (19.2)
ISS disease staging (initial)
I	5 (19.2)
II	17 (65.4)
III	4 (15.4)
ISS disease staging (at relapse)
I	13 (50.0)
II	11 (42.3)
III	2 (7.7)
Cytogenetic profile
High-risk cytogenetic abnormality	5 (19.2)
Del17p	2 (7.7)
t(4;14)	3 (11.5)
t(14;16)	3 (11.5)
Extramedullary skeletal disease	6 (23.1)
ECOG performance score
0	14 (53.8)
1	11 (42.3)
2	1 (3.8)
Time since initial diagnosis (yr), median (range)	2.4 (0.6-16.4)
Previous autologous stem-cell transplantation	12 (46.2)
1st line treatment
VTD	11 (42.3)
VMP	8 (30.7)
Rd	6 (23.1)
CMP	1 (3.8)
Prior bortezomib	19 (73.1)
Previous immunomodulatory drug therapy	18 (69.2)
Prior thalidomide	11 (42.3)
Prior lenalidomide	7 (26.9)
Lenalidomide refractory/exposed	6 (23.1)/7 (26.9)
Maintenance therapy	5 (19.2)

CMP, cyclophosphamide, melphalan, and prednisone; ECOG, Eastern Cooperative Oncology Group; Rd, lenalidomide and dexamethasone; VMP, bortezomib, melphalan, and prednisone; VTD, bortezomib, thalidomide, and dexamethasone.

Table 2.

Response and MRD-negativity rates

Response category	No. with response (%)
CR or better	10 (38.5)
sCR	2 (7.7)
CR	8 (30.7)
VGPR or better	17 (65.4)
VGPR	7 (26.9)
PR	5 (19.2)
MR	2 (7.7)
SD	2 (7.7)
PD	0
MRD1-negativity (10^-5)	n=13
Negative	6/13 (46.2)
MRD2-negativity (10^-5)	n=5 (+5)
Negative	2/5 (40.0)

CR, complete response; MR, minimal response; MRD, minimal residual disease; PD, progressive disease; PR, partial response; sCR, stringent complete response; SD, stable disease; VGPR, very good partial response.

Table 3.

The most common adverse events

Adverse events	Any grade	Grade 1-2	Grade 3-5
Common hematologic adverse event
Thrombocytopenia	24 (92.3)	20 (76.9)	4 (15.4)
Anemia	18 (69.2)	17 (65.4)	1 (3.8)
Neutropenia	18 (69.2)	18 (69.2)	0
Lymphopenia	19 (73.1)	9 (34.6)	10 (38.5)
Common non-hematologic adverse event
Fever	9 (34.6)	6 (23.1)	3 (11.5)
Peripheral neuropathy	5 (19.2)	4 (15.4)	1 (3.8)
Anorexia	4 (15.4)	2 (7.7)	-
Constipation	4 (15.4)	4 (15.4)	-
Upper respiratory tract infection	4 (15.4)	3 (11.5)	1 (3.8)
Diarrhea	3 (11.5)	2 (7.7)	1 (3.8)
Fatigue	3 (11.5)	3 (11.5)	-
Infusion related reaction	3 (11.5)	2 (7.7)	1 (3.8)
Pneumonia	3 (11.5)	3 (11.5)	-
Rash	3 (11.5)	3 (11.5)	-
COVID-19 infection	2 (7.7)	1 (3.8)	1 (3.8)
Sepsis	1 (3.8)	-	1 (3.8)

Values are presented as number (%). COVID-19, coronavirus disease 2019.

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A Phase II Study of Daratumumab in Combination with Bortezomib and Dexamethasone in Patients with Multiple Myeloma Who Received One Prior Line of Therapy (KMM1906)

DOI: https://doi.org/10.4143/crt.2025.426

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Abstract
Introduction
Materials and Methods
Results
Discussion
Electronic Supplementary Material
NOTES
REFERENCES

A Phase II Study of Daratumumab in Combination with Bortezomib and Dexamethasone in Patients with Multiple Myeloma Who Received One Prior Line of Therapy (KMM1906)

Fig. 1. The CONSORT diagram of patient flow (A) and response and swimmer plot of progression-free survival (B). CR, complete response; MR, minimal response; MRD, minimal residual disease; PR, partial response; sCR, stringent complete response; SD, stable disease; VGPR, very good partial response.

Fig. 2. Kaplan-Meier estimates of progression-free survival (A) and overall survival (B).

Fig. 3. Kaplan-Meier estimates progression-free survival (A) and overall survival (B) by minimal residual disease (MRD) status.

Fig. 1.

Fig. 2.

Fig. 3.

A Phase II Study of Daratumumab in Combination with Bortezomib and Dexamethasone in Patients with Multiple Myeloma Who Received One Prior Line of Therapy (KMM1906)

Characteristic	No. (%) (n=26)
Age (yr), median (range)	72 (47-85)
< 65	8 (30.7)
65-74	12 (46.2)
≥ 75	6 (23.1)
≤ 70 vs. ≥ 71	12 (46.2) vs. 14 (53.8)
Type of measurable disease
IgG	15 (57.7)
IgA	6 (23.1)
Detected in serum free light-chains only	5 (19.2)
ISS disease staging (initial)
I	5 (19.2)
II	17 (65.4)
III	4 (15.4)
ISS disease staging (at relapse)
I	13 (50.0)
II	11 (42.3)
III	2 (7.7)
Cytogenetic profile
High-risk cytogenetic abnormality	5 (19.2)
Del17p	2 (7.7)
t(4;14)	3 (11.5)
t(14;16)	3 (11.5)
Extramedullary skeletal disease	6 (23.1)
ECOG performance score
0	14 (53.8)
1	11 (42.3)
2	1 (3.8)
Time since initial diagnosis (yr), median (range)	2.4 (0.6-16.4)
Previous autologous stem-cell transplantation	12 (46.2)
1st line treatment
VTD	11 (42.3)
VMP	8 (30.7)
Rd	6 (23.1)
CMP	1 (3.8)
Prior bortezomib	19 (73.1)
Previous immunomodulatory drug therapy	18 (69.2)
Prior thalidomide	11 (42.3)
Prior lenalidomide	7 (26.9)
Lenalidomide refractory/exposed	6 (23.1)/7 (26.9)
Maintenance therapy	5 (19.2)

Response category	No. with response (%)
CR or better	10 (38.5)
sCR	2 (7.7)
CR	8 (30.7)
VGPR or better	17 (65.4)
VGPR	7 (26.9)
PR	5 (19.2)
MR	2 (7.7)
SD	2 (7.7)
PD	0
MRD1-negativity (10^-5)	n=13
Negative	6/13 (46.2)
MRD2-negativity (10^-5)	n=5 (+5)
Negative	2/5 (40.0)

Adverse events	Any grade	Grade 1-2	Grade 3-5
Common hematologic adverse event
Thrombocytopenia	24 (92.3)	20 (76.9)	4 (15.4)
Anemia	18 (69.2)	17 (65.4)	1 (3.8)
Neutropenia	18 (69.2)	18 (69.2)	0
Lymphopenia	19 (73.1)	9 (34.6)	10 (38.5)
Common non-hematologic adverse event
Fever	9 (34.6)	6 (23.1)	3 (11.5)
Peripheral neuropathy	5 (19.2)	4 (15.4)	1 (3.8)
Anorexia	4 (15.4)	2 (7.7)	-
Constipation	4 (15.4)	4 (15.4)	-
Upper respiratory tract infection	4 (15.4)	3 (11.5)	1 (3.8)
Diarrhea	3 (11.5)	2 (7.7)	1 (3.8)
Fatigue	3 (11.5)	3 (11.5)	-
Infusion related reaction	3 (11.5)	2 (7.7)	1 (3.8)
Pneumonia	3 (11.5)	3 (11.5)	-
Rash	3 (11.5)	3 (11.5)	-
COVID-19 infection	2 (7.7)	1 (3.8)	1 (3.8)
Sepsis	1 (3.8)	-	1 (3.8)

Table 1. Baseline characteristics

Table 2. Response and MRD-negativity rates

Table 3. The most common adverse events

Values are presented as number (%). COVID-19, coronavirus disease 2019.