OpenOnco · Treatment Plan

Treatment plan — DIS-MM

PLAN-BMA-CCND1_IHC_MM-V1 · v1 · 2026-05-04

Patient

BMA-CCND1_IHC_MM · Algorithm: ALGO-MM-1L

Clinical significance of mutations (ESCAT)

Tumor-board context — the engine does not use these tiers to rank tracks

Biomarker	Variant	ESCAT	Evidence	Clinical significance	Drugs	Sources
BIO-CCND1-IHC	CCND1 expression / cyclin D1 IHC (often surrogate for t(11;14))	IIA	SRC-NCCN-MM-2025 Evidence cited from clinical guidelines; per-source evidence levels not yet structured. See Phase-2-of-CIViC-pivot for re-cite roadmap.	CCND1 (cyclin D1) overexpression in MM strongly correlates with t(11;14) and BCL2 dependence — predicts venetoclax response. Used as surrogate when FISH unavailable.	venetoclax + dexamethasone (off-label, t(11;14)-surrogate)	SRC-NCCN-MM-2025
BIO-T11-14-IGH-CCND1	t(11;14)(q13;q32) IGH/CCND1	IIA	SRC-NCCN-MM-2025 SRC-ESMO-MM-2023 Evidence cited from clinical guidelines; per-source evidence levels not yet structured. See Phase-2-of-CIViC-pivot for re-cite roadmap.	t(11;14) myeloma (~15-20%) — distinct biology with high BCL2/MCL1 ratio. Venetoclax monotherapy (M14-032; Kumar Blood 2017 ORR ~40%) and venetoclax + dexamethasone (BELLINI subgroup; Kumar Lancet Oncol 2020) active. BELLINI raised mortality signal in non-t(11;14) arm — venetoclax is now t(11;14)-selected in MM. CANOVA Ph3 (venetoclax + dex vs pomalidomide + dex in t(11;14) R/R MM) read out 2024.	venetoclax + dexamethasone (R/R t(11;14)-selected, off-label NCCN-supported) venetoclax + carfilzomib + dex (NCT trials)	SRC-NCCN-MM-2025 SRC-ESMO-MM-2023

Treatment options (2 tracks)

Standard plan

★ DEFAULT

Indication

IND-MM-1L-VRD

Regimen

Bortezomib + Lenalidomide + Dexamethasone (VRd), 4-6 induction cycles

Drugs + NSZU

Bortezomib (DRUG-BORTEZOMIB) 1.3 mg/m² · SC days 1, 8, 15 of each 28-day cycle (weekly schedule for induction) · SC ⚠ NSZU — not for this indication
Lenalidomide (DRUG-LENALIDOMIDE) 25 mg · PO days 1-21 of each 28-day cycle · PO ⚠ NSZU — not for this indication
Dexamethasone (DRUG-DEXAMETHASONE) 40 mg (20 mg if age >75 or frail) · PO days 1, 8, 15, 22 of each 28-day cycle · PO ✓ NSZU covered

Supportive care

SUP-HSV-PROPHYLAXIS, SUP-MM-VTE-PROPHYLAXIS, SUP-MM-BONE-PROTECTION

Hard contraindications

CI-LENALIDOMIDE-PREGNANCY, CI-BORTEZOMIB-SEVERE-NEUROPATHY

Reason

Engine default per algorithm ALGO-MM-1L: {'step': 3, 'outcome': False, 'branch': {'result': 'IND-MM-1L-VRD'}, 'fired_red_flags': [], 'winner_red_flag': None}

Aggressive plan

Indication

IND-MM-1L-DVRD

Regimen

Daratumumab + Bortezomib + Lenalidomide + Dexamethasone (D-VRd), 4-6 induction cycles

Drugs + NSZU

Daratumumab (DRUG-DARATUMUMAB) 1800 mg SC (or 16 mg/kg IV) · weekly cycles 1-2 (days 1, 8, 15, 22), every 2 weeks cycles 3-6 (days 1, 15) · SC ⚠ NSZU — not for this indication
Bortezomib (DRUG-BORTEZOMIB) 1.3 mg/m² · SC days 1, 8, 15 of each 28-day cycle · SC ⚠ NSZU — not for this indication
Lenalidomide (DRUG-LENALIDOMIDE) 25 mg · PO days 1-21 of each 28-day cycle · PO ⚠ NSZU — not for this indication
Dexamethasone (DRUG-DEXAMETHASONE) 40 mg (20 mg if age >75 or frail; given before daratumumab as part of premedication) · PO/IV days 1, 8, 15, 22 of each 28-day cycle · PO ✓ NSZU covered

Supportive care

SUP-HSV-PROPHYLAXIS, SUP-MM-VTE-PROPHYLAXIS, SUP-MM-BONE-PROTECTION, SUP-PJP-PROPHYLAXIS

Hard contraindications

CI-LENALIDOMIDE-PREGNANCY, CI-BORTEZOMIB-SEVERE-NEUROPATHY, CI-HBV-NO-PROPHYLAXIS

Reason

Alternative track presented for HCP consideration

Pre-treatment investigations

Investigations before treatment start · critical / standard / desired · merged across tracks

ID	Name	Priority	Category	Where to order	Needed for
TEST-BM-ASPIRATE	Bone Marrow Aspirate	Critical	histology	—	all tracks
TEST-BM-TREPHINE	Bone Marrow Trephine	Critical	histology	—	all tracks
TEST-CBC	Complete Blood Count with Differential	Critical	lab	—	all tracks
TEST-CMP	Comprehensive Metabolic Panel	Critical	lab	—	all tracks
TEST-FISH-PANEL	FISH (Fluorescence In Situ Hybridization)	Critical	genomic	CSD Lab ✓ (code TBC)	all tracks
TEST-FREE-LIGHT-CHAINS	Serum Free Light Chains	Critical	lab	—	all tracks
TEST-HBV-SEROLOGY	Hepatitis B Serology Panel (HBsAg, anti-HBc total, anti-HBs)	Critical	lab	—	all tracks
TEST-LDH	Lactate Dehydrogenase	Critical	lab	—	all tracks
TEST-LFT	Liver Function Tests (ALT, AST, bilirubin, ALP, GGT, albumin)	Critical	lab	—	all tracks
TEST-SPEP-UPEP	SPEP / UPEP with IFE	Critical	lab	—	all tracks
TEST-WHOLE-BODY-MRI	Whole-Body MRI	Critical	imaging	—	all tracks
TEST-B2-MICROGLOBULIN	Beta-2 Microglobulin	Standard	lab	—	all tracks
TEST-ECHO	Echocardiography	Standard	imaging	—	aggressive
TEST-IMMUNOGLOBULINS	Quantitative Immunoglobulins	Standard	lab	—	all tracks

Red flags — PRO / CONTRA aggressive

PRO-AGGRESSIVE

Triggers that push toward the aggressive track

Multiple myeloma with ISS stage 3 — β2-microglobulin ≥5.5 mg/L — high-risk presentation; supports four-drug daratumumab-anchored 1L and transplant pursuit when feasible; trigger for R-ISS / R2-ISS upgrade with cytogeneticsRF-ISS-3
Multiple myeloma high-risk cytogenetics: any of t(4;14), t(14;16), t(14;20), del(17p)/TP53 loss, gain or amplification of 1q21 by interphase FISH on CD138-enriched plasma cellsRF-MM-HIGH-RISK-CYTOGENETICS
Aggressive plasma-cell biology indicating need for intensified MM induction: plasma cell leukemia (≥5% circulating plasma cells, or absolute count ≥500/µL), extramedullary disease at diagnosis (soft-tissue plasmacytoma not contiguous with bone), or rapid laboratory progression (≥25% rise in M-protein over 4-8 weeks pre-treatment). RF-MM-TRANSFORMATION-PROGRESSION
Multiple myeloma with R-ISS stage 3 — ISS-3 (β2M ≥5.5) PLUS LDH above ULN PLUS high-risk cytogenetics by FISH (any of t(4;14), t(14;16), del(17p)) — most aggressive presentation; supports four-drug D-VRd induction + ASCT (eligible) or D-Rd intensification (unfit) + maintenanceRF-R-ISS-3-HIGH-RISK

CONTRA-AGGRESSIVE

Hard contraindications to escalation

Lenalidomide is a potent teratogen — pregnancy is an absolute contraindication. Adequate contraception (two methods) and pregnancy testing are mandatory throughout therapy and for ≥4 weeks after discontinuation.CI-LENALIDOMIDE-PREGNANCY
Severe pre-existing peripheral neuropathy is an absolute contraindication to bortezomib — therapy will likely worsen the neuropathy to a disabling and often permanent extent.CI-BORTEZOMIB-SEVERE-NEUROPATHY
Active or latent HBV without antiviral prophylaxis is an absolute contraindication to starting B-cell-depleting / immunomodulatory monoclonal antibody therapy (anti-CD20, anti-CD30 ADC, anti-CD38). Severe HBV reactivation hepatitis risk including fulminant hepatic failure.CI-HBV-NO-PROPHYLAXIS

What NOT to do

Explicit prohibitive rules, each grounded in a regimen / supportive care / contraindication entity

Standard plan (IND-MM-1L-VRD)

Do not skip VTE prophylaxis (aspirin 81-100 mg or LMWH) — baseline thrombosis risk on lenalidomide is 10-20%, with prophylaxis falls to 2-5%.
Do not skip HSV/VZV prophylaxis (acyclovir 400 mg BID) during proteasome inhibitor — ~10-15% herpes zoster reactivation without prophylaxis.
Do not use IV bortezomib if SC is available — frequency of severe neuropathy is approximately twice as high with IV administration.
Do not start regimen in women of reproductive age without confirmed two methods of contraception + negative pregnancy test (lenalidomide is a potent teratogen).
Do not prescribe zoledronate without prior dental evaluation — risk of osteonecrosis of the jaw.
Do not skip lenalidomide dose reduction at CrCl 30-60 mL/min (10 mg) — full dose is toxic with renal impairment.

Aggressive plan (IND-MM-1L-DVRD)

Do not prescribe daratumumab without prior red-cell phenotyping (type and screen) — anti-CD38 interferes with direct Coombs and crossmatching.
Do not start without HBV screening + entecavir prophylaxis in HBsAg+ or anti-HBc+ — risk of HBV reactivation significantly elevated on anti-CD38.
Do not confirm D-VRd plan without verified funding pathway — daratumumab is NOT reimbursed via NSZU; the patient must be informed before the plan is announced.
Do not skip VTE prophylaxis (aspirin/LMWH) — IMiD-induced VTE risk is not reduced by adding daratumumab.
Do not skip HSV/VZV prophylaxis — bortezomib + dara combination increases immunosuppression.
Do not skip PJP prophylaxis — anti-CD38 + IMiD + steroid = elevated risk of opportunistic infections.
Do not start in women of reproductive age without two methods of contraception (lenalidomide is teratogenic).

Monitoring schedule

Monitoring schedule by treatment phase

Standard plan · MON-VRD-REGIMEN

Phase	Window	Tests	Checkpoints
baseline	Within 2 weeks before cycle 1	TEST-CBC, TEST-CMP, TEST-LFT, TEST-LDH, TEST-B2-MICROGLOBULIN, TEST-IMMUNOGLOBULINS, TEST-SPEP-UPEP, TEST-FREE-LIGHT-CHAINS, TEST-HBV-SEROLOGY, TEST-FISH-PANEL, TEST-BM-ASPIRATE, TEST-BM-TREPHINE, TEST-WHOLE-BODY-MRI, TEST-ECHO	Confirm CD138+ plasma cell percentage and FISH cytogenetic risk category R-ISS / R2-ISS staging documented Confirm HBV status and prophylaxis plan if anti-CD38 or anti-CD20 in regimen Dental evaluation before zoledronate / denosumab Red-cell phenotyping BEFORE first daratumumab dose
on_treatment	Day 1 of every 28-day cycle + mid-cycle CBC for high-risk patients	TEST-CBC, TEST-CMP, TEST-LFT, TEST-FREE-LIGHT-CHAINS, TEST-SPEP-UPEP	ANC ≥ 1000/µL and platelets ≥ 75K before each cycle (delay or reduce otherwise) Neuropathy grade documented at each visit (NCCN/CTCAE) Renal function trend (lenalidomide dose adjustment if CrCl drops) Glucose monitoring for steroid-induced hyperglycemia
response_assessment	After cycles 2 and 4 (before transplant) or every 2-3 cycles (transplant-ineligible)	TEST-FREE-LIGHT-CHAINS, TEST-SPEP-UPEP, TEST-IMMUNOGLOBULINS, TEST-BM-ASPIRATE, TEST-WHOLE-BODY-MRI	IMWG response criteria (sCR, CR, VGPR, PR, MR, SD, PD) MRD assessment by flow cytometry or NGS at suspected CR If <PR after cycle 2 → consider regimen change or trial enrollment
post_transplant_consolidation	Cycles 5-6 post-transplant (transplant-eligible only)	TEST-CBC, TEST-CMP, TEST-FREE-LIGHT-CHAINS, TEST-SPEP-UPEP	Recovery of counts post-transplant before consolidation start Confirm depth of response before starting maintenance
maintenance	Lenalidomide 10-15 mg daily until progression or intolerance	TEST-CBC, TEST-CMP, TEST-FREE-LIGHT-CHAINS, TEST-SPEP-UPEP	Surveillance for second primary malignancies (annual skin / GU exam) Lenalidomide dose adjustment if cytopenias or worsening renal function Annual influenza + pneumococcal vaccination (non-live only)
progression_monitoring	On clinical or biochemical progression	TEST-FREE-LIGHT-CHAINS, TEST-SPEP-UPEP, TEST-BM-ASPIRATE, TEST-FISH-PANEL, TEST-WHOLE-BODY-MRI	IMWG progression criteria (>25% increase in M-protein, new lytic lesions, hypercalcemia, etc.) Re-do FISH on relapse — high-risk clones may emerge

Timeline

Treatment timeline — derived from regimen + monitoring schedule

Standard plan

Baseline

Within 2 weeks before cycle 1

Induction · Bortezomib + Lenalidomide + De

28-day cycles × 4 cycles before stem-cell harvest (transplant-eligible) OR 8-12 cycles total (transplant-ineligible)

Response assessment

After cycles 2 and 4 (before transplant) or every 2-3 cycles (transplant-ineligible)

Maintenance

Lenalidomide 10-15 mg daily until progression or intolerance

Aggressive plan

Baseline

Within 2 weeks before cycle 1

Induction · Daratumumab + Bortezomib + Len

28-day cycles × 4 cycles before stem-cell harvest (transplant-eligible) OR 6 cycles induction + maintenance (transplant-ineligible per MAIA-style schedule)

Response assessment

After cycles 2 and 4 (before transplant) or every 2-3 cycles (transplant-ineligible)

Maintenance

Lenalidomide 10-15 mg daily until progression or intolerance

MDT brief

Skills (recommended) — for consideration (1)

Clinical pharmacist recommended
Chemoimmunotherapy regimen — drug-drug interactions, dose adjustments, premedication.
skill: clinical_pharmacistv0.1.0reviewed 2026-04-25STUBsign-offs: 0lead: TBD

Open questions (1, 0 blocking)

OQ-LDH-CURRENT
What is the current LDH? Marker of tumor burden and transformation.
LDH is part of the prognostic indices of indolent lymphomas.
→ hematologist

Data quality

Unevaluated RedFlags: RF-ISS-1, RF-ISS-3, RF-MM-BCMA-EXPRESSION-POS, RF-MM-CD38-EXPRESSION-DARA-CANDIDATE, RF-MM-CORD-COMPRESSION, RF-MM-FRAILTY-AGE, RF-MM-HIGH-RISK-CYTOGENETICS, RF-MM-HYPERCALCEMIA, RF-MM-HYPERVISCOSITY, RF-MM-INFECTION-SCREENING, RF-MM-RENAL-DYSFUNCTION, RF-MM-T11-14-ACTIONABLE, RF-MM-TRANSFORMATION-PROGRESSION, RF-R-ISS-3-HIGH-RISK

Skill catalog (1/16 activated in this plan)

All registered virtual specialists. ✓ — activated for this case; ○ — not activated (available for other clinical scenarios).

Specialist	skill_id	Version	Last reviewed	Domain
Cellular therapy specialist (CAR-T)	`cellular_therapy_specialist`	v0.1.0	2026-04-25	cellular_therapy
Clinical pharmacist	`clinical_pharmacist`	v0.1.0	2026-04-25	clinical_pharmacy
Hematologist / oncohematologist	`hematologist`	v0.1.0	2026-04-25	hematology_oncology
Hematopathologist (lymphoma / leukemia / myeloma)	`hematopathologist`	v0.1.0	2026-04-25	hematopathology
Infectious disease / hepatology	`infectious_disease_hepatology`	v0.1.0	2026-04-25	infectious_diseases
Medical oncologist (solid-tumor chemotherapist)	`medical_oncologist`	v0.1.0	2026-04-25	solid_oncology
Molecular geneticist / molecular oncologist	`molecular_geneticist`	v0.1.0	2026-04-25	molecular_oncology
Palliative care	`palliative_care`	v0.1.0	2026-04-25	palliative_care
Pathologist (general)	`pathologist`	v0.1.0	2026-04-25	pathology
Primary care / family physician	`primary_care`	v0.1.0	2026-04-25	primary_care
Psycho-oncologist	`psychologist`	v0.1.0	2026-04-25	psychosocial
Radiation oncologist	`radiation_oncologist`	v0.1.0	2026-04-25	radiation_oncology
Radiologist	`radiologist`	v0.1.0	2026-04-25	diagnostic_imaging
Social worker / case manager	`social_worker_case_manager`	v0.1.0	2026-04-25	psychosocial
Surgical oncologist	`surgical_oncologist`	v0.1.0	2026-04-25	surgical_oncology
Transplant specialist (BMT)	`transplant_specialist`	v0.1.0	2026-04-25	cellular_therapy

Sources cited

SRC-NCCN-MM-2025: NCCN Clinical Practice Guidelines in Oncology: Multiple Myeloma (v.X.2025)

Experimental options (clinical trials)

Last synced: 2026-05-04 · ctgov.

No active trials matched this scenario in ctgov.

Option availability in Ukraine

Per-track UA registration · NSZU · cost · access pathway. Render-time metadata; engine selection does not depend on these fields (CHARTER §8.3).

Option	UA registration	NSZU	Cost orientation	Access pathway
Standard plan Bortezomib + Lenalidomide + Dexamethasone (VRd), 4-6 induction cycles (REG-VRD)	✓ registered	✓ covered	₴-? — verify pathway	NSZU formulary
Aggressive plan Daratumumab + Bortezomib + Lenalidomide + Dexamethasone (D-VRd), 4-6 induction cycles (REG-DARA-VRD)	✓ registered	✓ covered	₴-? — verify pathway	NSZU formulary

Cost information is orientation. Verify with a specific pharmacy / foundation / trial site. Status updated: 2026-05-04.

plan_id: PLAN-BMA-CCND1_IHC_MM-V1 | version: 1 | generated: 2026-05-04T14:13:16.583171+00:00

Per FDA non-device CDS positioning (CHARTER §15): Outpatient oncology treatment planning to support tumor-board discussion. Not a medical device; not for autonomous clinical decision-making.

Per FDA non-device CDS positioning (CHARTER §15): Both treatment options below are presented for review. The engine's selection of a 'recommended' default does not constitute a clinical decision. Final treatment selection requires HCP judgment incorporating information not available to the system.

This document is an informational resource supporting tumor-board discussion (per CHARTER §11). It is not a system that makes clinical decisions. Every recommendation must be verified by the treating physician.