Treatment plan

OpenOnco · Treatment Plan

Treatment plan — DIS-MM

PLAN-MM-HR-001-V1 · v1 · 2026-04-27

Patient

MM-HR-001 · Algorithm: ALGO-MM-1L

Clinical significance of mutations (ESCAT / OncoKB)

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

Biomarker	Variant	ESCAT	OncoKB	Clinical significance	Drugs	Sources
No clinically actionable variants matched in this profile.

Treatment options (2 tracks)

Aggressive plan

★ DEFAULT

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

Engine default per algorithm ALGO-MM-1L: {'step': 1, 'outcome': True, 'branch': {'result': 'IND-MM-1L-DVRD'}, 'fired_red_flags': ['RF-MM-HIGH-RISK-CYTOGENETICS'], 'winner_red_flag': 'RF-MM-HIGH-RISK-CYTOGENETICS'}

Standard plan

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

Alternative track presented for HCP consideration

Why this branch was chosen

Triggers from the patient profile that fired and drove the chosen branch.

Step 1 → branch IND-MM-1L-DVRD

RF-MM-HIGH-RISK-CYTOGENETICS ★ winner: 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 cells SRC-NCCN-MM-2025SRC-ESMO-MM-2023

Pre-treatment investigations

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

ID	Name	Priority	Category	Needed for
TEST-BM-ASPIRATE	Аспірат кісткового мозку (цитологія + flow + цитогенетика + молекулярка)	Critical	histology	all tracks
TEST-BM-TREPHINE	Трепанобіопсія кісткового мозку (core-біопсія)	Critical	histology	all tracks
TEST-CBC	Загальний аналіз крові з лейкоцитарною формулою	Critical	lab	all tracks
TEST-CMP	Розширений біохімічний аналіз крові	Critical	lab	all tracks
TEST-FISH-PANEL	FISH-панель (специфічна для нозології)	Critical	genomic	all tracks
TEST-FREE-LIGHT-CHAINS	Вільні легкі ланцюги сироватки (kappa, lambda, співвідношення)	Critical	lab	all tracks
TEST-HBV-SEROLOGY	Серологія HBV: HBsAg, anti-HBc, anti-HBs	Critical	lab	all tracks
TEST-LDH	Лактатдегідрогеназа (ЛДГ)	Critical	lab	all tracks
TEST-LFT	Печінкові проби (АЛТ, АСТ, білірубін, ЛФ, ГГТП, альбумін)	Critical	lab	all tracks
TEST-SPEP-UPEP	Електрофорез білків сироватки та сечі з імунофіксацією	Critical	lab	all tracks
TEST-WHOLE-BODY-MRI	МРТ всього тіла (або низькодозова КТ всього тіла)	Critical	imaging	all tracks
TEST-B2-MICROGLOBULIN	Бета-2-мікроглобулін	Standard	lab	all tracks
TEST-ECHO	Ехокардіографія (ТТЕ) з оцінкою ФВ ЛШ	Standard	imaging	aggressive
TEST-IMMUNOGLOBULINS	Кількісні імуноглобуліни (IgG, IgA, IgM)	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

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

Не призначати daratumumab без попереднього red-cell phenotyping (type and screen) — анти-CD38 інтерферує з прямим Coombs та crossmatching.
Не починати без HBV скринінгу + entecavir prophylaxis при HBsAg+ або anti-HBc+ — ризик HBV реактивації значно підвищений на анти-CD38.
Не підтверджувати D-VRd план без верифікованого funding pathway — daratumumab НЕ реімбурсується через НСЗУ; пацієнт повинен бути попереджений до оголошення плану.
Не пропускати VTE профілактику (aspirin/LMWH) — IMiD-induced VTE ризик не зменшується від додавання даратумумабу.
Не пропускати HSV/VZV профілактику — комбінація bortezomib + dara підвищує immunosuppression.
Не пропускати PJP профілактику — анти-CD38 + IMiD + steroid = підвищений ризик опортуністичних інфекцій.
Не розпочинати у жінок репродуктивного віку без двох методів контрацепції (леналідомід — тератоген).

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

Не пропускати VTE профілактику (aspirin 81-100 mg або LMWH) — baseline ризик тромбозу на леналідоміді 10-20%, з профілактикою падає до 2-5%.
Не пропускати HSV/VZV профілактику (acyclovir 400 mg BID) під час інгібітору протеасоми — ~10-15% реактивації herpes zoster без профілактики.
Не використовувати IV bortezomib якщо доступний SC — частота важкої нейропатії приблизно вдвічі вища при IV введенні.
Не починати схема у жінок репродуктивного віку без підтверджених двох методів контрацепції + негативного тесту на вагітність (леналідомід — потужний тератоген).
Не призначати zoledronate без попередньої стоматологічної оцінки — ризик osteonecrosis of the jaw.
Не пропускати редукцію дози леналідоміду при CrCl 30-60 mL/min (10 mg) — повна доза токсична при renal impairment.

Monitoring schedule

Monitoring schedule by treatment phase

Aggressive 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

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

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

MDT brief

Skills (recommended) — for consideration (1)

Клінічний фармацевт recommended
Хіміоімунотерапевтичний схема — 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
Який актуальний LDH? Маркер пухлинного навантаження і трансформації.
LDH входить у прогностичні індекси індолентних лімфом.
→ hematologist

Data quality

Unevaluated RedFlags: RF-ISS-1, RF-ISS-3, 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-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
Specialist з клітинної терапії (CAR-T)	`cellular_therapy_specialist`	v0.1.0	2026-04-25	cellular_therapy
Клінічний фармацевт	`clinical_pharmacist`	v0.1.0	2026-04-25	clinical_pharmacy
Гематолог / онкогематолог	`hematologist`	v0.1.0	2026-04-25	hematology_oncology
Гематопатолог (специфічно для лімфом / лейкозів / мієломи)	`hematopathologist`	v0.1.0	2026-04-25	hematopathology
Інфекціоніст / гепатолог	`infectious_disease_hepatology`	v0.1.0	2026-04-25	infectious_diseases
Медичний онколог (хіміотерапевт солідних пухлин)	`medical_oncologist`	v0.1.0	2026-04-25	solid_oncology
Молекулярний генетик / молекулярний онколог	`molecular_geneticist`	v0.1.0	2026-04-25	molecular_oncology
Паліативна допомога	`palliative_care`	v0.1.0	2026-04-25	palliative_care
Патолог (загальний)	`pathologist`	v0.1.0	2026-04-25	pathology
Сімейний лікар / терапевт	`primary_care`	v0.1.0	2026-04-25	primary_care
Психолог / онкопсихолог	`psychologist`	v0.1.0	2026-04-25	psychosocial
Радіотерапевт (променева терапія)	`radiation_oncologist`	v0.1.0	2026-04-25	radiation_oncology
Лікар-радіолог	`radiologist`	v0.1.0	2026-04-25	diagnostic_imaging
Соціальний працівник / кейс-менеджер	`social_worker_case_manager`	v0.1.0	2026-04-25	psychosocial
Хірург-онколог	`surgical_oncologist`	v0.1.0	2026-04-25	surgical_oncology
Specialist з трансплантації (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)

Експериментальні опції (клінічні дослідження)

Третій трек плану — open-enrollment trials з ClinicalTrials.gov. Останнє оновлення: 2026-04-26. Render-time metadata; engine selection не змінюється цим блоком (CHARTER §8.3).

NCT	Name	Phase	Статус	Спонсор	UA
NCT05737732	The Ambient Light Multiple Myeloma Study	NA	RECRUITING	Icahn School of Medicine at Mount Sinai	—
NCT06896916	Study of Intravenously (IV) Infused Etentamig in Combination With an Oral Cereblon E3 Ligase Modulatory Drug (CELMoD) Agent Assessing Adverse Events and Change in Disease Activity in Adult Participants With Relapsed or Refractory Multiple Myeloma	PHASE1	RECRUITING	AbbVie	—
NCT05552222	A Study of Teclistamab in Combination With Daratumumab and Lenalidomide (Tec-DR) and Talquetamab in Combination With Daratumumab and Lenalidomide (Tal-DR) in Participants With Newly Diagnosed Multiple Myeloma	PHASE3	RECRUITING	Janssen Research & Development, LLC	—
NCT06270888	Hypofractionation (Radiation) Trial for Multiple Myeloma	PHASE1	RECRUITING	University of Chicago	—
NCT06145581	Remote Monitoring With Health-Coaching to Improve Quality of Life in Older Patients With Multiple Myeloma	NA	RECRUITING	Mayo Clinic	—
NCT05243212	Study of CAR-BCMA, a Chimeric Antigen Receptor T Cell (CAR-T) Therapy Directed Against BCMA in Subjects With Multiple Myeloma	PHASE1 / PHASE2	RECRUITING	Sheba Medical Center	—
NCT06182696	OriCAR-017 Chimeric Antigen Receptor (CAR) Modified T Cells for the Treatment of R/RMM	PHASE1 / PHASE2	RECRUITING	OriCell Therapeutics Co., Ltd.	—
NCT06636552	An Investigator-Initiated, Phase II, Multicenter, Open-Label, Single-Arm, Prospective Clinical Trial to Evaluate the Efficacy and Safety of Alternating Bortezomib-Based Regimens in Combination With DaratUMumab Followed by Maintenance With Daratumumab in the Frontline Setting of Primary Plasma CEll L	PHASE2	RECRUITING	Hellenic Society of Hematology	—
NCT07052916	A Music Therapy Study for Blood Cancer Survivors With Cognitive Difficulties	NA	RECRUITING	Memorial Sloan Kettering Cancer Center	—
NCT07489534	Study of PD-1Ab21-BCMA CAR-T Therapy for Consolidation of Multiple Myelomawith Renal Dysfunction	PHASE2	RECRUITING	Daihong Liu	—

Перевіряти статус набору безпосередньо у дослідницькому центрі. Дані ctgov можуть відставати від поточного статусу UA-сайтів.

Доступність опцій в Україні

Per-track UA registration · НСЗУ · cost · access pathway. Render-time metadata; engine selection не залежить від цих полів (CHARTER §8.3).

Опція	Реєстрація UA	НСЗУ	Cost orientation	Access pathway
Aggressive plan Daratumumab + Bortezomib + Lenalidomide + Dexamethasone (D-VRd), 4-6 induction cycles (REG-DARA-VRD)	✓ зареєстровано	✓ покривається	₴-? — verify pathway	НСЗУ formulary
Standard plan Bortezomib + Lenalidomide + Dexamethasone (VRd), 4-6 induction cycles (REG-VRD)	✓ зареєстровано	✓ покривається	₴-? — verify pathway	НСЗУ formulary
Trial · NCT05737732 The Ambient Light Multiple Myeloma Study No UA site listed — international referral required	— невідомо	— невідомо	self-pay: ₴0/course	Trial sponsor
Trial · NCT06896916 Study of Intravenously (IV) Infused Etentamig in Combination With an Oral Cereblon E3 Ligase Modulatory Drug (CELMoD) Agent Assessing Adverse Events and Change in Disease Activity in Adult Participants With Relapsed or Refractory Multiple Myeloma No UA site listed — international referral required	— невідомо	— невідомо	self-pay: ₴0/course	Trial sponsor
Trial · NCT05552222 A Study of Teclistamab in Combination With Daratumumab and Lenalidomide (Tec-DR) and Talquetamab in Combination With Daratumumab and Lenalidomide (Tal-DR) in Participants With Newly Diagnosed Multiple Myeloma No UA site listed — international referral required	— невідомо	— невідомо	self-pay: ₴0/course	Trial sponsor
Trial · NCT06270888 Hypofractionation (Radiation) Trial for Multiple Myeloma No UA site listed — international referral required	— невідомо	— невідомо	self-pay: ₴0/course	Trial sponsor
Trial · NCT06145581 Remote Monitoring With Health-Coaching to Improve Quality of Life in Older Patients With Multiple Myeloma No UA site listed — international referral required	— невідомо	— невідомо	self-pay: ₴0/course	Trial sponsor
Trial · NCT05243212 Study of CAR-BCMA, a Chimeric Antigen Receptor T Cell (CAR-T) Therapy Directed Against BCMA in Subjects With Multiple Myeloma No UA site listed — international referral required	— невідомо	— невідомо	self-pay: ₴0/course	Trial sponsor
Trial · NCT06182696 OriCAR-017 Chimeric Antigen Receptor (CAR) Modified T Cells for the Treatment of R/RMM No UA site listed — international referral required	— невідомо	— невідомо	self-pay: ₴0/course	Trial sponsor
Trial · NCT06636552 An Investigator-Initiated, Phase II, Multicenter, Open-Label, Single-Arm, Prospective Clinical Trial to Evaluate the Efficacy and Safety of Alternating Bortezomib-Based Regimens in Combination With DaratUMumab Followed by Maintenance With Daratumumab in the Frontline Setting of Primary Plasma CEll L No UA site listed — international referral required	— невідомо	— невідомо	self-pay: ₴0/course	Trial sponsor
Trial · NCT07052916 A Music Therapy Study for Blood Cancer Survivors With Cognitive Difficulties No UA site listed — international referral required	— невідомо	— невідомо	self-pay: ₴0/course	Trial sponsor
Trial · NCT07489534 Study of PD-1Ab21-BCMA CAR-T Therapy for Consolidation of Multiple Myelomawith Renal Dysfunction No UA site listed — international referral required	— невідомо	— невідомо	self-pay: ₴0/course	Trial sponsor

Інформація про ціни — orientation. Перевіряти у конкретній аптеці / foundation / трайл-сайті. Status updated: 2026-04-27.

plan_id: PLAN-MM-HR-001-V1 | version: 1 | generated: 2026-04-27T10:14:01.311958+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.