Doxorubicin
Adriamycin · Anthracycline
Experimental podocyte model; clinical proteinuria rare.
GLOM
MildOpen →
BCR-ABL1 tyrosine kinase inhibitor (3rd generation)
Olverembatinib
Olverembatinib (HQP1351) · BCR-ABL TKI
Potent T315I-active TKI with a largely renal-sparing profile
Mild2021 China approval; global phase 3 (POLARIS) program ongoing 2023-2026 · approved 2021
Chronic-phase CML with the T315I mutation after prior TKI therapyAccelerated-phase CML with the T315I mutationChronic-phase CML resistant or intolerant to first- and second-generation TKIsInvestigational: Ph+ ALL, succinate-dehydrogenase-deficient GIST (POLARIS program)
Signature kidney injury
Glomerular Injury / Proteinuria
Renal-specific data are sparse. In the Chinese phase 1/2 program (n=165) proteinuria was among the common treatment-related adverse events, though grade and exact rate were not separately quantified; clinically significant AKI was not a prominent signal. Direct nephrotoxicity appears low overall.
Source: Proteinuria listed among common treatment-related AEs in the phase 1/2 trial (Jiang Q et al., J Hematol Oncol 2022; PMID 35982483).
Toxicity fingerprint
Tap a signature to trace where it strikes the nephron.
Incidence not quantified
SeverityMild
ReversibilityVariable
Evidence0 refs
Nephron map
GlomerulusFiltration barrier (podocytes + endothelium)
Vasculature / Endothelium
Proximal Tubule
Glomerular Injury / Proteinuria
Damage to the filtration barrier — podocyte injury, FSGS and protein leak from VEGF and mTOR blockade.
Mechanism of kidney injury
No direct tubulotoxic mechanism is established. The plausible renal signature is glomerular/podocyte injury and VEGF-pathway-type effects (proteinuria, hypertension) shared with multi-kinase BCR-ABL TKIs such as ponatinib, arising from off-target inhibition of VEGFR/PDGFR signaling important to glomerular endothelial-podocyte homeostasis. A critical interpretive caveat: the most frequent laboratory abnormality is elevated blood creatine phosphokinase (CPK) — a skeletal-muscle marker, not a kidney marker — which must not be misread as renal injury, though severe CPK rise raises a theoretical pigment/rhabdomyolysis concern. Any small creatinine rise in the absence of true GFR loss could also reflect transporter-mediated (pseudo-AKI) effects, but this is inferred from class rather than proven for olverembatinib.
Clinical presentation
Most patients have no clinically apparent kidney disease. When present, the renal footprint is low-grade proteinuria, occasionally with treatment-emergent hypertension. Frank AKI, nephrotic-range proteinuria, or electrolyte wasting were not characteristic in registrational data. Elevated CPK (often asymptomatic, sometimes with myalgia) is common and is a muscular, not renal, finding.
Anticancer mechanism
Orally bioavailable third-generation BCR-ABL1 tyrosine kinase inhibitor that potently inhibits native BCR-ABL1 and a broad spectrum of resistance mutants, including the gatekeeper T315I mutation and compound mutations. It binds the ATP pocket of the ABL1 kinase domain, halting constitutive kinase signaling that drives Philadelphia-chromosome-positive CML and ALL. Like ponatinib, it has multi-kinase activity (including against VEGFR/PDGFR-family and KIT), which underlies both its broad efficacy and its off-target vascular and podocyte-relevant effects.
Management
For low-grade proteinuria, monitor with serial UACR and manage blood pressure (RAAS blockade where appropriate); dose interruption/reduction is reserved for worsening or nephrotic-range proteinuria, mirroring ponatinib-class practice. Treat treatment-emergent hypertension per standard guidelines. Marked CPK elevation should prompt evaluation for myopathy/rhabdomyolysis rather than being treated as primary kidney injury; ensure adequate hydration if pigment nephropathy is a concern. There is no agent-specific renal antidote; supportive care and hematology/nephrology co-management apply.Lesion-level management framework
Risk factors
- Pre-existing hypertension or chronic kidney disease
- Pre-existing proteinuria
- Prior or concurrent VEGF-pathway inhibitor exposure
- Heavily pretreated patients (prior ponatinib/asciminib) with cumulative vascular risk
- Volume depletion or concurrent nephrotoxins
Prevention
- Baseline and periodic urinalysis/UACR and blood-pressure monitoring
- Optimize blood pressure before and during therapy
- Distinguish CPK elevation (muscle) from creatinine/renal markers when interpreting labs
- Maintain euvolemia and minimize concurrent nephrotoxins
Note · No dedicated nephrotoxicity study of olverembatinib exists as of mid-2026; this profile reasons conservatively from registrational safety data and BCR-ABL/multi-kinase TKI class behavior. Educational content, not medical advice.
Clinical depth
Renal dose adjustment
Standard dosing is 30-40 mg orally every other day (30 mg for non-T315I per the phase 1b recommended dose; 40 mg the RP2D in the Chinese program). No validated renal-impairment dose adjustment has been published; pharmacokinetics support alternate-day dosing, and a high-fat meal substantially increases exposure (Cmax +106%, AUC +70%), so administration relative to food should be consistent. Use clinical caution in significant renal impairment given limited data.
Dialyzability & ESKD dosing
Unknown / not characterized. As a small-molecule TKI that is highly protein-bound and lipophilic with a large apparent volume of distribution, it is unlikely to be appreciably removed by hemodialysis, but no formal data exist.
Differential diagnosis
Distinguish drug-related glomerular proteinuria from CML-related or unrelated causes (diabetic/hypertensive nephropathy, paraproteins). Critically, separate an isolated CPK rise (skeletal-muscle origin, very common with olverembatinib) from true renal injury. Consider prerenal/hemodynamic AKI from volume depletion or concurrent nephrotoxins, and TLS-related urate nephropathy in high-burden disease at initiation.
Monitoring
- Baseline and periodic urinalysis / urine albumin-to-creatinine ratio
- Serum creatinine and electrolytes
- Blood pressure at each visit
- Creatine phosphokinase (CPK) — interpret as muscle, not kidney
- Tumor lysis labs (urate, K, phosphate, calcium) at initiation in high-burden disease
Key trials & series
- Phase 1/2 China registrational program in T315I and TKI-resistant CML (NCT03883087, NCT03883100; Jiang Q et al., J Hematol Oncol 2022, PMID 35982483)
- Phase 1b global bridging RCT after >=2 TKIs including ponatinib/asciminib failure (NCT04260022; Jabbour E et al., JAMA Oncol 2025, PMID 39570620)
- POLARIS-1/-2/-3 phase 3 registrational program (NCT06051409, NCT06423911, NCT06640361)
Clinical pearls
- The dominant lab abnormality is elevated CPK (~39% all-grade in the global phase 1b) — a muscle marker, NOT a sign of kidney injury; do not confuse it with creatinine.
- Proteinuria is the recurring renal signal, consistent with VEGF/multi-kinase class effects shared with ponatinib.
- Direct nephrotoxicity and frank AKI were not prominent in registrational data — treat the renal profile as largely sparing but monitor proteinuria and blood pressure.
- A high-fat meal markedly increases exposure (AUC +70%); keep food timing consistent to avoid swings that could amplify off-target effects.
- Renal-specific literature is essentially absent; renal expectations are reasoned from class and from registrational safety data, and should be revisited as POLARIS phase 3 data mature.
Beyond the kidney
Class-level context for the major non-renal toxicities of bcr-abl1 tyrosine kinase inhibitor (3rd generation)s.
Vascular
Hypertension, VTE/ATE, bleeding, aneurysm
- Vascular occlusion (ponatinib), fluid retention
Pulmonary
Pneumonitis, ILD, effusions, hypertension
- Pleural effusions (dasatinib), PAH
Cardiac
Cardiomyopathy, QT, ischemia, myocarditis
- QT, heart failure
Evidence
4 peer-reviewed references. Citation metadata via PubMed / NLM.
LandmarkOlverembatinib (HQP1351), a well-tolerated and effective tyrosine kinase inhibitor for patients with T315I-mutated chronic myeloid leukemia: results of an open-label, multicenter phase 1/2 trial.Jiang Q et al. · Journal of Hematology & Oncology 2022 · PMID 35982483Pivotal Chinese phase 1/2 registrational program (n=165); lists proteinuria among common treatment-related adverse events — the principal renal signal — alongside hyperpigmentation, hypertriglyceridemia, and thrombocytopenia.PMIDOlverembatinib After Failure of Tyrosine Kinase Inhibitors, Including Ponatinib or Asciminib: A Phase 1b Randomized Clinical Trial.Jabbour E et al. · JAMA Oncology 2025 · PMID 39570620Global phase 1b bridging RCT; documents elevated blood creatine phosphokinase (CPK) as the most frequent treatment-emergent AE (39% all-grade, 13% grade >=3) — a muscle, not renal, marker that is commonly misread; informs dosing and overall tolerability.PMIDOlverembatinib in chronic myeloid leukemia-Review of historical development, current status, and future research.Kantarjian H et al. · Cancer 2025 · PMID 40197896Authoritative review of mechanism, approval status, tolerability, and the ongoing POLARIS phase 3 program; supports the class-based, largely renal-sparing framing and broad multi-kinase activity.PMIDEffects of a High-Fat Meal on the Pharmacokinetics of Olverembatinib in Patients With Chronic Myeloid Leukemia.Wang H et al. · Clinical and Translational Science 2026 · PMID 42105274Food-effect pharmacokinetic study showing a high-fat meal raises Cmax ~106% and AUC ~70%, relevant to consistent dosing and exposure-dependent off-target effects; confirms the alternate-day PK profile.
Related agents
Other agents sharing the same signature kidney injury.