MedPath

A Study of Subcutaneous Versus (vs.) Intravenous Administration of Daratumumab in Participants With Relapsed or Refractory Multiple Myeloma

Phase 3
Completed
Conditions
Multiple Myeloma
Interventions
Drug: Dara SC
Drug: Dara IV
Registration Number
NCT03277105
Lead Sponsor
Janssen Research & Development, LLC
Brief Summary

The purpose of this study is to show that subcutaneous (SC) administration of daratumumab co-formulated with recombinant human hyaluronidase PH20 (Dara SC) is non-inferior to intravenous (IV) administration of daratumumab (Dara IV) in terms of the overall response rate (ORR) and maximum trough concentration (Ctrough).

Detailed Description

The study population will consist of adults diagnosed with multiple myeloma who have received at least 3 prior lines of therapy including a proteasome inhibitor (PI) and an immunomodulatory drug (IMiD), or whose disease is refractory to both a PI and an IMiD. The study consists of 3 phases: a screening phase (up to 28 days), a treatment phase, and a follow-up phase. Efficacy, pharmacokinetics, immunogenicity, biomarkers and safety will be assessed at scheduled time. Follow-up will continue until the end of the data collection period, approximately 24 months after the last participant was randomized or when the median overall survival for both arms has been reached, whichever occurs first. The primary hypotheses is that the ORR and maximum Ctrough for Dara SC 1800 milligram (mg) are not inferior to the ORR and maximum Ctrough, respectively, for Dara IV 16 mg per kilogram (mg/kg) in participants with multiple myeloma who have received at least 3 prior lines of therapy including a proteasome inhibitor (PI) and an immunomodulatory drug (IMiD), or whose disease is refractory to both a PI and an IMiD.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
522
Inclusion Criteria
  • Evidence of a response (Partial response [PR] or better based on investigator's determination of response by international myeloma working group [IMWG] criteria) to at least 1 prior treatment regimen

  • Received at least 3 prior lines of therapy including a proteasome inhibitor (PI) (greater than or equal to [>=] 2 cycles or 2 months of treatment) and an immunomodulatory drug (IMiD) (>=2 cycles or 2 months of treatment) in any order during the course of treatment (except for participants who discontinued either of these treatments due to a severe allergic reaction within the first 2 cycles/months). A single line of therapy may consist of 1 or more agents, and may include induction, hematopoietic stem cell transplantation, and maintenance therapy. Radiotherapy, bisphosphonate, or a single short course of corticosteroids (no more than the equivalent of dexamethasone 40 milligram/day [mg/day] for 4 days) would not be considered prior lines of therapy

  • Documented multiple myeloma as defined by the criteria below:

    1. Multiple myeloma diagnosis according to the IMWG diagnostic criteria

    2. Measurable disease at Screening as defined by any of the following:

      1. Serum M-protein level >=1.0 gram per deciliter (g/dL) or urine M-protein level >=200 mg/24 hours; or
      2. Light chain multiple myeloma without measurable disease in the serum or the urine: Serum immunoglobulin free light chain (FLC) >=10 mg/dL and abnormal serum immunoglobulin kappa lambda FLC ratio
  • Eastern Cooperative Oncology Group (ECOG) performance status score of 0, 1, or 2

  • Meet the clinical laboratory criteria as specified in the protocol

  • Women of childbearing potential must have a negative urine or serum pregnancy test at screening within 14 days prior to randomization

Read More
Exclusion Criteria
  • Received daratumumab or other anti-CD38 therapies previously
  • Received anti-myeloma treatment within 2 weeks or 5 pharmacokinetic half-lives of the treatment, whichever is longer, before the date of randomization. The only exception is emergency use of a short course of corticosteroids (equivalent of dexamethasone 40 mg/day for a maximum of 4 days) before treatment
  • Received autologous stem cell transplant within 12 weeks before the date of randomization, or the participant has previously received allogeneic stem cell transplant (regardless of timing)
  • Plans to undergo a stem cell transplant prior to progression of disease on this study (these participants should not be enrolled to reduce disease burden prior to transplant)
  • History of malignancy (other than multiple myeloma) unless all treatment of that malignancy was completed at least 2 years before consent and the patient has no evidence of disease. Further exceptions are squamous and basal cell carcinomas of the skin and carcinoma in situ of the cervix, or breast, or other non-invasive lesion, that in the opinion of the investigator, with concurrence with the sponsor's medical monitor, is considered cured with minimal risk of recurrence within 3 years
Read More

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Dara SCDara SCParticipants will receive a fixed dose of daratumumab as 1800 milligram (mg) subcutaneously (Dara SC) co-formulated with recombinant human hyaluronidase (rHuPH20) 2000 Unit per milliliter (U/mL), once weekly in Cycle 1 and 2, every 2 weeks in Cycle 3 to 6, every 4 weeks in Cycle 7 and thereafter until disease progression, unacceptable toxicity or the end of study. The duration for each cycle is 4 weeks.
Dara IVDara SCParticipants will receive daratumumab for intravenous infusion (Dara IV) 16 mg/kg once weekly in Cycle 1 and 2, every 2 weeks in Cycle 3 to 6, every 4 weeks on Day 1 in Cycle 7 and thereafter until disease progression, unacceptable toxicity or the end of study. The duration for each cycle is 4 weeks. For Participants still receiving treatment with Dara-IV at the time of Protocol Amendment 4 the duration of infusion may be shortened to a 90-minute infusion or participants will have the option to switch to Dara 1800 mg subcutaneous (SC) on Day 1 of any cycle, at the discretion of the investigator.
Dara IVDara IVParticipants will receive daratumumab for intravenous infusion (Dara IV) 16 mg/kg once weekly in Cycle 1 and 2, every 2 weeks in Cycle 3 to 6, every 4 weeks on Day 1 in Cycle 7 and thereafter until disease progression, unacceptable toxicity or the end of study. The duration for each cycle is 4 weeks. For Participants still receiving treatment with Dara-IV at the time of Protocol Amendment 4 the duration of infusion may be shortened to a 90-minute infusion or participants will have the option to switch to Dara 1800 mg subcutaneous (SC) on Day 1 of any cycle, at the discretion of the investigator.
Primary Outcome Measures
NameTimeMethod
Maximum Trough Concentration (Ctrough) of DaratumumabPredose on Cycle 3 Day 1 (each cycle of 28 days)

Maximum Ctrough was defined as the serum predose concentration of daratumumab on Cycle 3 Day 1.

Overall Response Rate (ORR)Up to 1 year 8 months

ORR was defined as the percentage of participants who achieved partial response (PR) or better according to International Myeloma Working Group (IMWG) criteria, during or after study treatment. IMWG criteria for PR: greater than or equal to (\>=) 50 percent (%) reduction of serum M-protein and reduction in 24-hour urinary M-protein by \>=90% or to less than (\<) 200 milligrams (mg)/24 hours, If the serum and urine M-proteins are not measurable, a decrease of \>=50% in the difference between involved and uninvolved free light chain (FLC) levels were required in place of the M-protein criteria, If serum and urine M-protein are not measurable, and serum free light assay was also not measurable, \>=50% reduction in bone marrow plasma cells (PCs) was required in place of M-protein, provided baseline bone marrow plasma cell percentage was \>=30%. In addition to the above criteria, if present at baseline, a \>=50% reduction in the size of soft tissue plasmacytomas was also required.

Secondary Outcome Measures
NameTimeMethod
Time to Next TherapyUp to 3 years

Time to next therapy was defined as the time from randomization to the start of the first subsequent anti-cancer therapy.

Progression Free Survival (PFS)Up to 3 years

PFS was defined as time from date of randomization to either progression of disease (PD), death due to any cause, whichever occurs first. IMWG criteria for PD: Increase of 25% from lowest response value in any one of the following: Serum M component (absolute increase must be \>=0.5 gram per deciliter (g/dL), Urine M-component (absolute increase must be \>=200 mg/24 hours), Participants without measurable serum and urine Mprotein levels: difference between involved and uninvolved free light chain (FLC) levels (absolute increase must be \>10 milligrams per deciliter (mg/dL), participants without measurable serum and urine M-protein levels and without measurable disease by FLC levels, bone marrow PC% (absolute percentage must be \>=10%), definite development of new bone lesions or soft tissue plasmacytomas or increase in size of bone lesions or tissue plasmacytomas and development of hypercalcemia (serum calcium \>11.5 mg/dL) that can be attributed solely to PC proliferative disorder.

Percentage of Participants With Complete Response (Including sCR) or BetterUp to 3 years

CR or better was defined as percentage of participants with a CR or better (CR or stringent complete response \[sCR\]) based on computerized algorithm as per IMWG criteria. IMWG criteria for CR- negative immunofixation on the serum and urine, and disappearance of any soft tissue plasmacytomas, and \<5% PCs in bone marrow. sCR: CR plus normal FLC ratio, and absence of clonal PCs by IHC, immunofluorescencea or 2- to 4 color flow cytometry.

Overall Survival (OS)Up to 3 years

OS was defined as the time from the date of randomization to the date of the participant's death due to any cause.

Percentage of Participants With Treatment-emergent Infusion-related Reactions (IRR)Up to 3 years

Percentage of participants with treatment-emergent infusion-related reactions were reported.

Time to Very Good Partial Response (VGPR) or BetterUp to 3 years

Time to VGPR or better was defined as the time from randomization until onset of first VGPR or better.

Percentage of Participants With Very Good Partial Response (VGPR) or BetterUp to 3 years

VGPR or better was defined as the percentage of participants who achieved VGPR or better (VGPR, complete response (CR) or stringent complete response \[sCR\]), based on computerized algorithm as per IMWG criteria during or after the study treatment. IMWG criteria for VGPR: Serum and urine M-component detectable by immunofixation but not on electrophoresis, or \>=90 percent (%) reduction in serum M-protein plus urine M-protein \<100 milligrams (mg)/24 hours, CR: Negative immunofixation on the serum and urine, disappearance of any soft tissue plasmacytomas and \<5% plasma cells (PCs) in bone marrow. sCR: CR plus normal FLC ratio, and absence of clonal PCs by immunohistochemistry (IHC), immunofluorescencea or 2- to 4 color flow cytometry.

Duration of ResponseUp to 3 years

Duration of response was defined as the duration from the date of initial documentation of a response (PR or better) to the date of first documented evidence of progressive disease according to the IMWG criteria. PD was defined as an increase of 25 % from the lowest response value in one of the following: serum and urine M-component (absolute increase must be \>= 0.5 g/dL and \>=200 mg/24 hours respectively); Only in participants without measurable serum and urine M-protein levels the difference between involved and uninvolved FLC levels (absolute increase must be \> 10 mg/dL); Definite development of new bone lesions or soft tissue plasmacytomas or definite increase in the size of existing bone lesions or soft tissue plasmacytomas; Development of hypercalcemia (corrected serum calcium \>11.5 mg/dL) that can be attributed solely to PC proliferative disorder.

Time to Partial Response (PR) or BetterUp to 3 years

Time to PR or better was defined as the time from randomization until onset of first response of PR or better.

Patient-Reported Satisfaction With Therapy as Assessed With Cancer Therapy Satisfaction Questionnaire (CTSQ)Cycle 1 (Days 8,15 and 22), Cycle 2 (Days 1,8,15 and 22), Cycle 3,4,5,6,7,8,9,10,11,12,13,14,15,16,17,18,19,20,21 and 22 (Day 1)

Modified-CTSQ contain 9 items (2 items for Thoughts about Cancer Therapy and 7 items in a defined domain of Satisfaction with Therapy) specific to satisfaction with therapy and for comparison of SC and IV administration. Satisfaction with therapy was calculated based on 7-items using 5-point verbal rating scale, where 1= never and 5= always. Scores were averaged and transformed to a 0-100 scale; higher scores represent better health. At least 5 of the 7 items within the Satisfaction with Therapy domain had to be completed to calculate a domain score. No domain score was calculated for Thoughts about Cancer Therapy.

Time to Complete Response (CR) or BetterUp to 3 years

Time to CR or better was defined as the time from randomization until onset of first CR or better.

Trial Locations

Locations (146)

Azienda USL di Piacenza

🇮🇹

Piacenza, Italy

Levine Cancer Institute

🇺🇸

Charlotte, North Carolina, United States

Royal Prince Alfred Hospital

🇦🇺

Camperdown, Australia

St. Vincent's Hospital Melbourne

🇦🇺

Fitzroy, Australia

Fiona Stanley Hospital

🇦🇺

Murdoch, Australia

Sir Charles Gairdner Hospital

🇦🇺

Nedlands, Australia

Hospital Das Clinicas Da Faculdade De Medicina Da USP

🇧🇷

São Paulo, Brazil

Calvary Mater Newcastle Hospital

🇦🇺

Waratah, Australia

Fundacao Pio XII

🇧🇷

Barretos, Brazil

Tom Baker Cancer Centre

🇨🇦

Calgary, Alberta, Canada

Fakultni nemocnice Brno

🇨🇿

Brno, Czechia

Fakultni nemocnice Kralovske Vinohrady

🇨🇿

Praha 10, Czechia

Fakultní nemocnice Olomouc

🇨🇿

Olomouc, Czechia

Vseobecna fakultni nemocnice v Praze - I. interni klinika - klinika hematologie

🇨🇿

Praha 2, Czechia

Royal Marsden Hospital

🇬🇧

Surrey, United Kingdom

Ospedale Villa Sofia-Cervello

🇮🇹

Palermo, Italy

Fondazione IRCCS Policlinico San Matteo

🇮🇹

Pavia, Italy

CHU Caen - Côte de Nacre

🇫🇷

Caen, France

Hillel Yaffe Medical Center - Oncology

🇮🇱

Hadera, Israel

Rambam Med.Center - Hematology Institute

🇮🇱

Haifa, Israel

Chugoku Central Hospital

🇯🇵

Fukuyama, Japan

CHU Poitiers - Hôpital la Milétrie

🇫🇷

Poitiers, France

Università di Roma La Sapienza

🇮🇹

Roma, Italy

Sheba Medical Center Tel Hashomer

🇮🇱

Ramat Gan, Israel

Policlinico Sant'Orsola Malpighi

🇮🇹

Bologna, Italy

Tel Aviv Sourasky Medical Center

🇮🇱

Tel Aviv, Israel

A.O.U. Città della Salute e della Scienza

🇮🇹

Torino, Italy

Ogaki Municipal Hospital

🇯🇵

Gifu, Japan

Fukuoka University Hospital

🇯🇵

Fukuoka, Japan

Iwate Medical University Hospital

🇯🇵

Iwate, Japan

Gachon University Gil Medical Center

🇰🇷

Incheon, Korea, Republic of

Severance Hospital

🇰🇷

Seoul, Korea, Republic of

Asan Medical Center

🇰🇷

Seoul, Korea, Republic of

Szpital Uniwersytecki w Krakowie

🇵🇱

Krakow, Poland

Samodzielny Publiczny Szpital Kliniczny nr 1 w Lublinie

🇵🇱

Lublin, Poland

Hosp. Quiron Madrid Pozuelo

🇪🇸

Pozuelo de Alarcon, Spain

State Institution 'National Scientific Center for Radiation Medicine of NAMS of Ukraine'

🇺🇦

Kiev, Ukraine

Falu Lasarett

🇸🇪

Falun, Sweden

Hosp. Univ. Dr. Peset

🇪🇸

Valencia, Spain

Clinica Univ. de Navarra

🇪🇸

Pamplona, Spain

Helsingborgs lasarett

🇸🇪

Helsingborg, Sweden

Akademiska Sjukhuset

🇸🇪

Uppsala, Sweden

CHU de Boreaux

🇫🇷

Pessac, France

Centre hospitalier Lyon-Sud

🇫🇷

Pierre-Bénite, France

CHU Nancy Brabois

🇫🇷

Vandoeuvre Les Nancy, France

Kobe City Medical Center General Hospital

🇯🇵

Hyogo, Japan

Matsuyama Red Cross Hospital

🇯🇵

Matsuyama, Japan

Japanese Red Cross Nagoya Daini Hospital

🇯🇵

Nagoya, Japan

Osaka University Hospital

🇯🇵

Osaka, Japan

Nagoya City University Hospital

🇯🇵

Nagoya, Japan

Hospital das Clinicas de Porto Alegre

🇧🇷

Porto Alegre, Brazil

Centro de Pesquisa e Ensino em Oncologia de Santa Catarina - CEPEN

🇧🇷

Florianopolis, Brazil

Instituto de Educacao, Pesquisa e Gestao em Saude

🇧🇷

Rio de Janeiro, Brazil

Cross Cancer Institute

🇨🇦

Edmonton, Alberta, Canada

Victoria Hospital

🇨🇦

London, Ontario, Canada

QEII Health Sciences Centre

🇨🇦

Halifax, Nova Scotia, Canada

CHU de Québec -L'Hôtel-Dieu de Québec

🇨🇦

Québec, Quebec, Canada

Penza Regional Oncology Dispensary

🇷🇺

Penza, Russian Federation

National Cancer Center

🇰🇷

Goyang-Si, Korea, Republic of

Dana-Farber Cancer Institute

🇺🇸

Boston, Massachusetts, United States

Alfred Health

🇦🇺

Melbourne, Australia

Fundacao Doutor Amaral Carvalho

🇧🇷

Jau, Brazil

The Queen Elizabeth Hospital

🇦🇺

Woodville South, Australia

Associacao Hospitalar Beneficente Sao Vicente de Paulo - Hospital Sao Vicente de Paulo

🇧🇷

Passo Fundo, Brazil

Instituto Joinvilense de Hematologia e Oncologia Ltda-Centro de Hematologia e Oncologia

🇧🇷

Joinville, Brazil

CEHON

🇧🇷

Salvador, Brazil

Fundacao Faculdade Regional de Medicina de Sao Jose do Rio Preto - Hospital de Base

🇧🇷

Sao Jose do Rio Preto, Brazil

Clinica Sao Germano

🇧🇷

São Paulo, Brazil

Fakultni nemocnice Ostrava

🇨🇿

Ostrava, Czechia

The Gordon & Leslie Diamond Health Care Center

🇨🇦

Vancouver, British Columbia, Canada

Fakultni nemocnice Plzen, Hemato-onkologicke oddeleni

🇨🇿

Plzen, Czechia

Fakultni nemocnice Hradec Kralove

🇨🇿

Hradec Kralove, Czechia

Alexandra General Hospital of Athens

🇬🇷

Athens Attica, Greece

CHU de Nantes hotel Dieu

🇫🇷

Nantes Cedex 1, France

Hopital Claude Huriez

🇫🇷

Lille Cedex, France

Carmel Medical Center

🇮🇱

Haifa, Israel

Hadassah Medical Center

🇮🇱

Jerusalem, Israel

Rabin Medical Center Beilinson Campus

🇮🇱

Petah Tikva, Israel

Fondazione IRCCS Istituto Nazionale dei Tumori

🇮🇹

Milano, Italy

Policlinico Universitario Agostino Gemelli

🇮🇹

Roma, Italy

Gunma University Hospital

🇯🇵

Gunma, Japan

University Hospital Kyoto Perfectural University of Medicine

🇯🇵

Kyoto, Japan

National Hospital Organization Okayama Medical Center

🇯🇵

Okayama, Japan

Niigata Cancer Center Hospital

🇯🇵

Niigata, Japan

National Hospital Organization Sendai Medical Center

🇯🇵

Sendai-City, Japan

Pusan National University Hospital

🇰🇷

Busan, Korea, Republic of

Princess Alexandra Hospital

🇦🇺

Woolloongabba, Australia

Japanese Red Cross Medical Center

🇯🇵

Shibuya, Japan

National Hospital Organization Shibukawa Medical Center

🇯🇵

Shibukawa, Japan

Samsung Medical Center

🇰🇷

Seoul, Korea, Republic of

Szpital Specjalistyczny w Brzozowie Podkarpacki Osrodek Onkologiczny im Ks B Markiewicza

🇵🇱

Brzozow, Poland

Ulsan University Hospital

🇰🇷

Ulsan, Korea, Republic of

The Catholic University of Korea Seoul St. Mary's Hospital

🇰🇷

Seoul, Korea, Republic of

Szpitale Pomorskie Sp z o o

🇵🇱

Gdynia, Poland

Wojewodzki Szpital Specjalistyczny w Legnicy

🇵🇱

Legnica, Poland

S.P. Botkin Moscow City Clinical Hospital

🇷🇺

Moscow, Russian Federation

Emergency Hospital of Dzerzhinsk

🇷🇺

Dzerzhinsk, Russian Federation

City Clinical Hospital # 40

🇷🇺

Moscow, Russian Federation

Nizhniy Novgorod Region Clinical Hospital

🇷🇺

Nizny Novgorod, Russian Federation

Ryazan Regional Clinical Hospital

🇷🇺

Ryazan, Russian Federation

Saint Petersburg City Hospital #15

🇷🇺

Saint-Petersburg, Russian Federation

Samara Region Clinical Hospital

🇷🇺

Samara, Russian Federation

Mykolaiv Regional Clinical Hospital

🇺🇦

Mykolaiv, Ukraine

Ekaterinburg City Clinical Hospital # 7

🇷🇺

Ekaterinburg, Russian Federation

Clinical Research Institute of Hematology and Transfusiology

🇷🇺

St-Petersburg, Russian Federation

Hosp. Univ. Germans Trias I Pujol

🇪🇸

Badalona, Spain

Oncology Dispensary of Komi Republic

🇷🇺

Syktyvkar, Russian Federation

Hosp. Clinic de Barcelona

🇪🇸

Barcelona, Spain

Hosp. Univ. Dr. Josep Trueta

🇪🇸

Girona, Spain

Hosp. Univ. Virgen de Las Nieves

🇪🇸

Granada, Spain

Hosp. de Leon

🇪🇸

Leon, Spain

Hosp. Univ. de Canarias

🇪🇸

La Laguna, Spain

Hosp. Univ. 12 de Octubre

🇪🇸

Madrid, Spain

Hosp. Univ. Infanta Leonor

🇪🇸

Madrid, Spain

Hosp. Gral. Univ. Gregorio Maranon

🇪🇸

Madrid, Spain

Hosp. Clinico Univ. de Salamanca

🇪🇸

Salamanca, Spain

Karolinska University Hospital, Huddinge

🇸🇪

Huddinge, Sweden

Skanes universitetssjukhus

🇸🇪

Lund, Sweden

Norrlands University Hospital

🇸🇪

Umea, Sweden

China Medical University Hospital

🇨🇳

Taichung City, Taiwan

Taichung Veterans General Hospital

🇨🇳

Taichung,, Taiwan

SI Grigoriev Institute for Medical Radiology National Academy of Medical Science of Ukraine

🇺🇦

Kharkiv, Ukraine

Communal Nonprofit Enterprise 'Cherkasy Regional Oncology Dispensary Of Cherkasy Regional Council'

🇺🇦

Cherkasy, Ukraine

Dnepropetrovsk City Clinical Hospital #4, Regional Hematology Center

🇺🇦

Dnepropetrovsk, Ukraine

Ivano-Frankivsk Regional Clinical Hospital

🇺🇦

Ivano-Frankivsk, Ukraine

Kiev Marrow Transplantation Center, Bone Marrow Transplantation Department

🇺🇦

Kiev, Ukraine

National Cancer Institute, Dept. of chemotherapy of hemoblastosis

🇺🇦

Kiev, Ukraine

Blackpool Victoria Hospital

🇬🇧

Blackpool, United Kingdom

Leicester Royal Infirmary - Haematology

🇬🇧

Leicester, United Kingdom

Royal Bournemouth Hospital

🇬🇧

Bournemouth, United Kingdom

Ukrainian Medical Stomatological Academy, Poltava Regional Clinical Hospital

🇺🇦

Poltava, Ukraine

St Bartholomew's Hospital

🇬🇧

London, United Kingdom

Nottingham City Hospital

🇬🇧

Nottingham, United Kingdom

Guys St Thomas Hospital

🇬🇧

London, United Kingdom

Christie Hospital NHS Trust

🇬🇧

Manchester, United Kingdom

New Cross Hospital

🇬🇧

Wolverhampton, United Kingdom

Chang Gung Memorial Hospital

🇨🇳

Taoyuan, Taiwan

Samodzielny Publiczny Zaklad Opieki Zdrowotnej Zespol Szpitali Miejskich

🇵🇱

Chorzów, Poland

Chang-Hua Christian Hospital

🇨🇳

Changhua, Taiwan

Szpital Kliniczny Przemienienia Panskiego Uniwersytetu Medycznego im. Karola Marcinkowskiego

🇵🇱

Poznan, Poland

Szpital Uniwersytecki nr 2 im. Jana Biziela w Bydgoszczy

🇵🇱

Bydgoszcz, Poland

Narodowy Instytut Onkologii im Marii Sklodowskiej Curie Panstwowy Instytut Badawczy

🇵🇱

Warszawa, Poland

National Cheng Kung University Hospital

🇨🇳

Tainan, Taiwan

National Taiwan University Hospital

🇨🇳

Taipei, Taiwan

Institute of Blood Pathology and Transfusion Medicine of AMS of Ukraine

🇺🇦

Lviv, Ukraine

Princess Margaret Hospital

🇨🇦

Toronto, Ontario, Canada

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