Study to Evaluate Efficacy and Safety of Belantamab-based Combinations for Relapsed Multiple Myeloma (GEM-BELACOMBOS)

Retrospective Observational Study to Evaluate the Effectiveness and Safety of Belantamab Mafodotin-based Combinations (Belantamab Mafodotin, Bortezomib, Dexamethasone [BVd] or Belantamab Mafodotin, Pomalidomide, Dexamethasone [BPd]) Used as Compassionate Use in Patients With Multiple Myeloma in First or Second Relapse

The goal of this retrospective observational study is to characterize multiple myeloma (MM) patients (by collecting demographics, disease characteristics and treatment history data) treated in first or second relapse with belantamab mafodotin combinations under compassionate use conditions.

The main question it aims to answer is which belantamab combinations (belantamab mafodotin+bortezomib+dexamethasone [BVd] vs. belantamab mafodotin+pomalidomide+dexamethasone [BPd]) show higher response rates in patients with MM in first or second relapse.

Study Overview

• Status: Not yet recruiting
• Conditions: Relapse Multiple Myeloma
• Intervention / Treatment: Drug: Belantamab mafodotin; Drug: Bortezomib; Drug: Dexamethasone; Drug: Pomalidomide

Detailed Description

This retrospective observational study will collect data from MM patients at first or second relapse to evaluate the response rates under belantamab mafodotin-based therapeutic shedules as salvage therapy.

Data from participants either treated with belantamab mafodotin+bortezomib+dexamethasone [BVd] or belantamab mafodotin+pomalidomide+dexamethasone [BPd] schedules will be evaluated. Data collection will include the following data:

• Sociodemographics (demographic data, disease status and clinical chracteristics).
• Medical history (MM diagnosis, disease characteristics and history of prior treatment with anti-MM therapies).
• Treatment with BVd or BPd (overall response rate, duration of response, progression-free survival at diagnosis, progression-free survival at relapse, duration of the treatment, overall survival, side effects, infections and concomitant treatments during the treatment with belantamab-based schedules).

Researchers will compare data from aprticipants treated with BVd or BPd to learn which belantamab-based combination shows higher response rates and which is safer by showing less adverse effects.

• Study Type: Observational
• Enrollment (Estimated): 100

Contacts and Locations

• Study Contact: Name: Carmen López-Carrero; Phone Number: +34916 26 62 32; Email: carmen@fundacionpethema.es

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: N/A

• Sampling Method: Non-Probability Sample

Study Population

Adult patients with Multiple Myeloma treated with combinations of belantamab mafodotin at first or second relapse, or refractory disease, not being in fourth or more lines of treatment.

Description

Inclusion Criteria:

• Confirmed diagnosis of relaps/refractory MM.
• Having received at least one dose of a belantamab mafodotin combination (BVd or BPd) under compassionate use conditions as treatment for a first or second relapse.
• Patients ≥18 years of age at the start of treatment with the belantamab mafodotin combination (BVd or BPd) under compassionate use conditions.

Exclusion Criteria:

• Any patient who has received a belantamab mafodotin combination (BVd or BPd) under compassionate use conditions in fourth line of treatment or later will be excluded from the study.

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Belantamab mafodotin+Bortezomib+dexamethasone (BVd); Participants receiving belantamab and dexametahsone plus the proteasome inhibitor Bortezomib as salvage therapy in first or second MM relapse.	Drug: Belantamab mafodotin; All participants evaluated in this study must have received this drug as salvage therapy in first or second relapse. Doses, dose reductions, increased spacing between doses and number of total infusions will be recorded.; Drug: Bortezomib; Participants in BVd arm must have received this drug in combination with belantamab mafodotin in first or second relapse. Doses, dose reductions, increased spacing between doses and number of total infusions will be recorded.; Drug: Dexamethasone; All participants evaluated in this study must have received this drug as salvage therapy in first or second relapse. Doses, dose reductions, increased spacing between doses and number of total infusions will be recorded.
Belantamab mafodotin+Pomalidomide-dexamethason (BPd); Participants receiving belantamab and dexametahsone plus the inmunomadulatory drug Pomalidomide as salvage therapy in first or second MM relapse.	Drug: Belantamab mafodotin; All participants evaluated in this study must have received this drug as salvage therapy in first or second relapse. Doses, dose reductions, increased spacing between doses and number of total infusions will be recorded.; Drug: Dexamethasone; All participants evaluated in this study must have received this drug as salvage therapy in first or second relapse. Doses, dose reductions, increased spacing between doses and number of total infusions will be recorded.; Drug: Pomalidomide; Participants in BPd arm must have received this drug in combination with belantamab mafodotin in first or second relapse. Doses, dose reductions, increased spacing between doses and number of total infusions will be recorded.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Patient year of birth	Measured in date (year)	18 months
Patient sex	Measured in male vs female	18 months
Patient weight	Measured in kilograms	18 months
Disease diagnosis date	Measured in date (dd/mm/yyyy)	18 months
Disease Interational Score System status at diagnosis	Developed in 2005 by the International Myeloma Working Group (IMWG), it uses two readily available blood tests (serum β2 microglobulin (Sβ2M) and serum albumin) to classify patients into three stages: Stage I: Sβ2M < 3.5 mg/L; serum albumin ≥ 3.5 g/dL. Stage II: Sβ2M < 3.5 mg/L; serum albumin < 3.5 g/dL; or β2M 3.5 to 5.5 mg/L, irrespective of serum albumin. Stage III: Sβ2M > 5.5 mg/L.	18 months
Disease type of MM (secretory or oligosecretory)	Defined as secretory (when immunoglobulines are detectable in the patient's serum and/or urine) or oligosecretory (when inmunoglobulines are below the treshold shown next). Secretory treshold definition: M-protein≥1 gr/dL, or U-PEP > 200 mg/24 hours or involved free light chain≥ 100 mg/L.	18 months
Disease type of immunoglobulin	Measures the type of immunoglobuline secreted by MM tumour cells (IgG, IgA, IgD, IgE or IgM)	18 months
Disease ECOG status	The ECOG Performance Status Scale describes a patient's level of functioning in terms of their ability to care for themself, daily activity, and physical ability (walking, working, etc.). Grades: 0: Fully active, able to carry on all pre-disease performance without restriction; Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature, e.g., light house work, office work; Ambulatory and capable of all selfcare but unable to carry out any work activities; up and about more than 50% of waking hours; Capable of only limited selfcare; confined to bed or chair more than 50% of waking hours; Completely disabled; cannot carry on any selfcare; totally confined to bed or chair; Dead	18 months
Disease extramedullar disease at relapse	Extramedullary disease is defined as an aggressive form of multiple myeloma characterized by the presence of soft-tissue plasmacytomas that result from hematogenous spread	18 months
Disease presentation of plasma cell leukemia	Plasma cell leukemia is a rare and aggressive variant of myeloma characterized by the presence of circulating plasma cells; diagnosis is based upon the percentage (≥20%) and absolute number (≥2 × 109/L) of plasma cells in peripheral blood. This outcome aims to annotate if the particpiant has a canonical MM (between 10% and 19% of clonal plasma cells in bone marrow) or the rare leukemized variant of MM, which is also known as plasma cell leukemia (≥20% clonal plasma cells).	18 months
Disease genetic risk	This outcome aims to annotate if the participant has high-genetic risk MM. High-genetic risk in MM (Avet-Loiseau H J Clin Oncol 2025) is defined as the presence of any of the following: Deletion of 17p in >20% of sorted plasma cells; TP53 mutation; Biallelic deletion of 1p32; 2 alterations of the following: t(4;14), t(14;16) or t(14,20); or Gain/amplification of 1q; or monoallelic del 1p32	18 months
Disease kidney function pre-belantamab infusion by creatinine clearance	This outcome aims to annotate if the participant shows kideny disfunction or impairment at any time during treatment. Kidney or renal impairment is defined as creatinine clearance below 40 mL/min due to myeloma.	18 months
Disease kidney function pre-belantamab infusion by serum creatinine	This outcome aims to annotate if the participant shows kideny disfunction or impairment at any time during treatment. Kidney or renal impairment can also be evaluated by serum creatinine and this happens when serum creatinine is above 2 mg/dL due to myeloma.	18 months
Disease kidney failure at disease progression	This outcome aims to annotate if the participant shows kidney failure at disease progression. Kidney failure is defined as an estimated glomerular filtration rate (eGFR) below 15 mL/min.	18 months
Disease tumoral load pre-belantamab infusion by circulating cells	Tumoral load refers to the amount of disease detected at any time. It will be measured by the number of circulating tumour cells in peripheral blood (cells/L).	18 months
Disease tumoral load pre-belantamab infusion by serum beta-2-microglobulin	Tumoral load refers to the amount of disease detected at any time. It will be measured by serum beta-2-microglobulin levels (mg/L)	18 months
Disease presence of lytic lesions	This outcome aims to annotate if the participant shows bone lytic lesions at any time during treatment. Lytic lesions are lesions that replace normal bone or with a vast proportion showing a lower density or attenuation than the normal bone. These lesions are characterized either by the replacement of bone matrix by other types of tissue including soft tissue, fluid or fat. These lytic lesions are caused by MM cells and are detected and accounted by radiography.	18 months
Disease previous anti-MM treatments	Annotation of the treatments received by each patient before the treatment with belantamab combinations analyzed in this study.	18 months
Disease number of previous anti-MM treatments and treatment response	Annotation of the number of treatments received by each patient before the treatment with belantamab combinations analyzed in this study, and what patients' duration of response was (defined in months).	18 months
Disease first line treatment	First line treatment refers to the treatment the patient received at diagnosis (in de novo MM status)	18 months
Disease date of first relapse	Measured in date (dd/mm/yyyy)	18 months
Disease date of second relapse (if applies)	Measured in date (dd/mm/yyyy)	18 months
Disease date of second line treatment (if applies)	Measured in date (dd/mm/yyyy)	18 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Type of treatment (BVd or BPd)	Defined as which belantamab combination the patient received (Belantamab+Bortezomib+dexamethasone [BVd], or Belantaman+Pomalidomide+dexamethaspone [BPd])	18 months
Incidence, grade and duration of side effects of belantamab mafodotin combinations (BVd and BPd) under compasionate use conditions	Data on incidence, grade, duration and type of infections will be collected, as well as the proportion of participants who required inmunoglobulin treatment during BVd or BPd.	18 months
Disease comorbidities	The appearance of any of the following will be annotated: Hypercalcemia; Kidney failure; Anemia; Bone problems, such as osteoporosis, bone pain, and fractures	18 months
Date of drug infusion	Measured in dd/mm/yyyy for each drug of the belantamab combinations	18 months
Drug dose	The dose of each drug of the belantamab combinations will be annotated	18 months
Dose reduction	Dose reductions for each drug of the belantamab combinations will be annotated	18 months
Reason for dose reduction	The reason for dose reductions for each drug of the belantamab combinations will be annotated	18 months
Drug delay	The time frame (in days) of any drug delay between drug doses for each drug of the belantamab combinations will be annotated	18 months
New interval between doses	The new time frame (in days) between doses of any drug for each drug of the belantamab combinations will be annotated	18 months
Survival data, Overall response rate	Defined as the percentage of patients with confirmed partial response or better (i.e., partial response, very good partial response, complte remission, and strict complete response), according to International Myeloma Working Group 2016 or later criteria, if possible, and clinician's notes otherwise.	18 months
Survival data, Duration of response	Defined as the time from first documented evidence of partial response or better to disease progression or death, among patients who achieved confirmed partial response or better.	18 months
Survival data, Progression-free survival	Defined as defined as the time in months from the first belantamab mafodotin infusion to the date of the first documented disease progression or death, whichever occurs first.	18 months
Survival data, Overall Survival	Defined as defined as the time from the first infusion of belantamab mafodotin (start date) until the date of death from any cause.	18 months
Survival data, Progression-free survival 2	Defined as time from the first infusion of belantamab mafodotin to the date of disease progression (second relapse) or death (whichever occurs first), documented after initiation of new anti-myeloma therapy.	18 months

Collaborators and Investigators

• Sponsor: PETHEMA Foundation
• Investigators: Study Chair: Javier de la Rubia, Hospital Universitario la Fe

Study record dates

Study Major Dates

• Study Start (Estimated): June 1, 2026
• Primary Completion (Estimated): December 31, 2027
• Study Completion (Estimated): December 31, 2027

Study Registration Dates

• First Submitted: May 27, 2026
• First Submitted That Met QC Criteria: June 4, 2026
• First Posted (Actual): June 9, 2026

Study Record Updates

• Last Update Posted (Actual): June 9, 2026
• Last Update Submitted That Met QC Criteria: June 4, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: belantamab mafodotin
• Additional Relevant MeSH Terms: Organic Chemicals; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Polycyclic Compounds; Inorganic Chemicals; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Steroids, Fluorinated; Pregnadienetriols; Boronic Acids; Acids, Noncarboxylic; Acids; Boron Compounds; Pyrazines; Bortezomib; Dexamethasone; pomalidomide; belantamab mafodotin
• Other Study ID Numbers: GEM-BELACOMBOS

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes