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

Belantamab mafodotin+Bortezomib+dexamethasone (BVd)

Participants receiving belantamab and dexametahsone plus the proteasome inhibitor Bortezomib as salvage therapy in first or second MM relapse.

Лекарство: 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.

Лекарство: 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.

Лекарство: 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.

Лекарство: 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.

Лекарство: 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.

Лекарство: 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.

Patient year of birth

Measured in date (year)

Patient sex

Measured in male vs female

Patient weight

Measured in kilograms

Disease diagnosis date

Measured in date (dd/mm/yyyy)

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.

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.

Disease type of immunoglobulin

Measures the type of immunoglobuline secreted by MM tumour cells (IgG, IgA, IgD, IgE or IgM)

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

1. 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
2. Ambulatory and capable of all selfcare but unable to carry out any work activities; up and about more than 50% of waking hours
3. Capable of only limited selfcare; confined to bed or chair more than 50% of waking hours
4. Completely disabled; cannot carry on any selfcare; totally confined to bed or chair
5. Dead

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

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).

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.

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.

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.

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).

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)

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.

Disease previous anti-MM treatments

Annotation of the treatments received by each patient before the treatment with belantamab combinations analyzed in this study.

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).

Disease first line treatment

First line treatment refers to the treatment the patient received at diagnosis (in de novo MM status)

Disease date of first relapse

Measured in date (dd/mm/yyyy)

Disease date of second relapse (if applies)

Measured in date (dd/mm/yyyy)

Disease date of second line treatment (if applies)

Measured in date (dd/mm/yyyy)

Disease high-risk

This outcome aims to annotate if the participant has high-risk MM.

High-risk MM can be measured by a) beta 2-microglobulin (Sβ2M) levels, or by b) tumour genetic alterations:

1. High-risk is considered when Sβ2M>=5.5mg/L (if creatinin <1.2mg/dL).

2. 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

Patient comorbidities

This outcome will annotate the patients' medical history before administering any belantamab combination including:

• Lung disease
• Heart disease
• Diabetes
• Other

Type of treatment (BVd or BPd)

Defined as which belantamab combination the patient received (Belantamab+Bortezomib+dexamethasone [BVd], or Belantaman+Pomalidomide+dexamethaspone [BPd])

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

Drug dose

The dose of each drug of the belantamab combinations will be annotated

Dose reduction

Dose reductions for each drug of the belantamab combinations will be annotated

Reason for dose reduction

The reason for dose reductions for each drug of the belantamab combinations will be annotated

Drug delay

The time frame (in days) of any drug delay between drug doses for each drug of the belantamab combinations will be annotated

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

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.

Date of drug infusion/administration

Measured in dd/mm/yyyy for each drug of the belantamab combinations

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.

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.

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.

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.

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.