Personalising Treatment for Myeloma Patients Based on Initial Response to NHS Treatment and Their Overall Fitness Level

Prior treatment

• Previous treatment for myeloma, except as specified in the protocol,
• Received systemic anti-myeloma therapy other than DRd prior to randomisation. Steroids given (by any route) for reasons other than myeloma disease control are allowed,
• Received a stem cell transplant,

Other illness

• Active systemic viral, fungal or bacterial infection requiring systemic therapy. Criteria for specific chronic infections clarified in the protocol, or
• Stable disease (SD) or progressive disease (PD) as per IMWG response criteria (iFIT1 and iFIT2),
• Partial response (PR), stable disease (SD) or progressive disease (PD) as per IMWG response criteria (iFIT3), and

Other

• Smouldering myeloma (SMM), primary amyloidosis, solitary plasmacytoma of bone or extramedullary plasmacytoma (without additional evidence of myeloma),
• Pregnant, breastfeeding, plans to become pregnant, or plans to father a child whilst enrolled in the study or within 3 months after the last dose,
• Participation in any other interventional study for myeloma that involves an IMP during treatment and active monitoring.
  • Additional eligibility criteria for randomisation into iFIT1/iFIT2/iFIT3 pathways, as follows:
• Participation in any other interventional study for myeloma that involves an IMP during treatment and active monitoring, and
• Pregnant, breast feeding, plans to become pregnant, or plans to father a child whilst enrolled in the study or within a specified period after the last dose.
• Further exclusion criteria related to safety of interventions (iFIT1).
  • Full inclusion and exclusion criteria are listed in the protocol.

• Newly diagnosed as having symptomatic MM, plasma cell leukaemia or non-secretory MM according to IMWG diagnostic criteria 2014.
• Considered not suitable to receive autologous stem cell transplant as part of their first line therapy by the treating clinician,
• Planned for treatment with Daratumumab, Lenalidomide and dexamethasone (DRd) as first line therapy as standard of care,
• Aged 18 years or greater,
• Able to provide full informed consent, and
• Prepared to comply with pregnancy prevention plan.
• Completed 6 cycles of DRd induction therapy after registering within the iFIT study,
• Able to provide full informed consent, and
• Prepared to comply with pregnancy prevention plan.
• Dexamethasone may have been stopped due to toxicity and the participant will remain eligible (iFIT1 and iFIT3),
• Planned to continue on at least daratumumab (monthly) and lenalidomide (at any dose level) (iFIT1 and iFIT3),
• Planned to continue on all three DRd medications (dose reductions are allowed) (iFIT2),
• Achieved a partial response (PR) biochemically (irrespective of MRD status) or achieved a ≥VGPR and are MRD positive, as confirmed by HMDS (central laboratory) (iFIT1 and iFIT2),
• Achieved a ≥VGPR and are MRD negative, as confirmed by HMDS (central laboratory) (iFIT3),
• Categorised as FIT or UNFIT according to the IMWG frailty index (iFIT1),
• Categorised as FRAIL according to the IMWG frailty index (iFIT2), and
• Meet the blood criteria specified in the protocol within 14 days before randomisation (haematological and biochemical) (iFIT1).

Criteria the registry did not label

• Eligibility criteria for registration: