International Journal of Hematology (2018) 107:460–467
Safety and ecacy of daratumumab in combination with bortezomib
and dexamethasone in Japanese patients with relapsed or refractory
· Tatsuo Ichinohe
· Atsushi Shinagawa
· Kenshi Suzuki
· Naoki Takezako
· Masayuki Aoki
Received: 31 August 2017 / Revised: 7 December 2017 / Accepted: 7 December 2017 / Published online: 19 December 2017
© The Japanese Society of Hematology 2017
Daratumumab in combination with bortezomib and dexamethasone (DVd) has demonstrated longer progression-free survival
than combination of bortezomib and dexamethasone in patients with relapsed or refractory multiple myeloma (RRMM). In
this multicenter, open-label, phase-1 study, the safety, eﬃcacy, and pharmacokinetics (PK) of DVd were evaluated in Japa-
nese patients with RRMM. Eight patients with RRMM aged between 54 and 82 years were enrolled and treated with DVd
regimen. Primary endpoints were tolerability and safety. Secondary endpoints were overall response rate (ORR), very good
partial response (VGPR) or better, complete response (CR) or better, time to response (TTR), PK, and immunogenicity. All
patients (n = 8) experienced Grade ≥ 3 treatment-emergent adverse events (TEAE), with thrombocytopenia (n = 6, 75%)
being the most frequent. Mild Grade ≤ 2 infusion-related reactions were reported in ﬁve patients. Serious TEAEs were herpes
zoster, nasopharyngitis, and prostate cancer (n = 1 each). Three dose-limiting toxicities were observed in two patients. No
death or disease progression was reported as of the study cut-oﬀ date. ORR was 100% (2 CRs or better, 2 VGPRs, 4 PRs).
The median TTR was 0.9 months. PK proﬁles were comparable to previous studies. The DVd regimen showed acceptable
safety with favorable eﬃcacy in Japanese patients with RRMM.
Clinical trial registration number NCT02497378.
Keywords Daratumumab · Eﬃcacy · Multiple myeloma · Safety · Tolerability
Multiple myeloma (MM) is an incurable malignancy of
plasma cells that is characterized by abnormal production
of monoclonal immunoglobin and distinctive organ dam-
ages, mainly aﬀecting bone tissues, hematopoietic system,
and kidneys . In Japanese population, the incidence of
MM has increased from 0.92 to 5.2 per 100,000 during
1975 to 2010 . Treatment outcomes in MM depend on
the factors related to biologic proﬁles of disease, comor-
bidity of patients, and type of treatment such as the use of
novel agents and autologous stem cell transplantation .
Although median overall survival of patients with MM
has signiﬁcantly improved subsequent to introduction of
newer therapies such as proteasome inhibitors (PIs)  and
immunomodulatory drugs (IMiDs), long-term prognosis is
still unsatisfactory [2, 5–7]. Also, elderly and frail patients
have poorer responses to the initial therapy and frequently
develop resistance to these agents [8, 9].
Previous publication: The abstract submitted to the JSH, 20–22th
October, 2017 in Yokohama, Japan.
Electronic supplementary material The online version of this
article (https://doi.org/10.1007/s12185-017-2390-2) contains
supplementary material, which is available to authorized users.
* Shinsuke Iida
Department of Hematology and Oncology, Nagoya City
University Graduate School of Medical Sciences, Nagoya,
Department of Hematology and Oncology, Research Institute
for Radiation Biology and Medicine, Hiroshima University,
Hitachi General Hospital, Hitachi, Japan
Department of Hematology, Japanese Red Cross Medical
Center, Tokyo, Japan
Department of Hematology, National Disaster Medical
Center of Japan, Tokyo, Japan
Janssen Pharmaceutical K.K., Tokyo, Japan