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"3 + 7" - Daunorubicin, cytarabine 

• Standard of care - all patients should receive "3 + 7" unless there is a compelling reason to receive the below regimens

• Considered an induction cycle - will receive for only one cycle

  • Patients stay in hospital until count recovery (~21-28 days following initiation of chemotherapy)

  • A day 14-bone marrow will be performed

    • If asplastic (no blasts and low cellularity) will start filgrastim

    • If persistent disease but with low blasts (~5-40%) and low cellularity (<10-20%) will not begin filgrastim but will perform another bone marrow biopsy in 1-2 weeks or wait for count recovery

    • If significant disease left on day 14 marrow will administer re-induction chemotherapy if medically able (usually with FLAG)

Decitabine + Venetoclax 

• For older patients unfit for 3+7 induction

• Used for induction, consolidation/maintenance, and re-induction

  • Both decitabine + venetoclax and FLAG or CLAG are appropriate for this patient population. Selection is based on patient preference

    • Hypomethylating agent + venetoclax is supported by a Phase III randomized controlled trial while FLAG is supported by internal data

    • Patients may elect to receive therapy as an outpatient (therefore select decitabine with venetoclax)

      • This can unfortunately take several months to attain a complete remission 

    • Patients may prefer a quicker remission (especially if the goal is an allo-transplant) thus select FLAG

• Although the pivotal Phase III trial utilized azacitidine (7 days) and venetoclax (400 mg for 28 days), we use decitabine (5-10 days depending on patient fitness) and venetoclax (100 mg for 14-21 days due to azole antifungal drug interaction and significant myelosuppression with this regimen)

  • Despite the package insert recommending a dose escalation and 70 mg of venetoclax when used with a strong CYP inhibitor, we use 100 mg with strong CYP inhibitors and do not employ a dose escalation (ie: 100 mg on day 1)

  • Most patients can be discharged after the decitabine is complete if no other medical needs and not requiring daily platelet transfusions

• Helpful resources:

  • Oral Chemotherapy Guidance

  • Venetoclax Dosing Guidance 

FLAG or CLAG 

• Used in patients who may not tolerate 3+7 (elderly patients with good kidney function, patients who received prior anthracyclines, secondary leukemias from prior MDS, myelofibrosis, polycythemia vera, essential thrombocytosis, CMML)

• FLAG is also our regimen of choice for relapsed/refractory patients

• First cycle will be induction cycle (chemo given for 5 days), subsequent cycles are consolidation (chemo given for 4 days)

• Due to a fludarabine shortage we also give CLAG (cladribine instead of fludarabine)

• A day 21 aplasia marrow will be performed; if counts appear to be recovering the day 21 bone marrow biopsy can be cancelled

• Patients stay in hospital until count recovery (~21 days following initiation of chemotherapy)

FLAG-IDA or CLAG-IDA

• Idarubicin added for relapsed/refractory patients who have relapsed at least > 6 months from last high dose ara-C dose and anthracycline

• When idarubicin is added, FLAG is shortened to 4 days

• Due to a fludarabine shortage we also give CLAG (cladribine instead of fludarabine)

• A day 21 aplasia marrow will be performed

• Patients stay in hospital until count recovery (~28 days following initiation of chemotherapy)

GCLAC

• For relapsed/refractory patients (chosen over FLAG when deemed healthy enough to tolerate)

• This regimen is more expensive, more toxic and lacks quality superiority data over FLAG or CLAG therefore it has fallen out of favor. 

• First cycle will be induction cycle (chemo given for 5 days), subsequent cycles are consolidation (chemo given for 4 days)

• A day 21 aplasia marrow will be performed

• Patients stay in hospital until count recovery (~28 days following initiation of chemotherapy)

MEC 

• For relapsed/refractory patients who have relapsed within 6 months from last high dose cytarabine consolidation

• A day 21 aplasia marrow will be performed

• Patients stay in hospital until count recovery (~28 days following initiation of chemotherapy)

High Dose Cytarabine Consolidation (HIDAC) 

• Consolidation chemotherapy after a patient has received 3+7 induction and achieved a remission

• Three main toxicities to note are 1) neurotoxicity from ara-UTP which can accumulate in older patients with renal dysfunction; patients do finger-to-nose test and sign their name daily to identify early signs of cerebellar toxicity 2) keratoconjunctivitis which patients will administer steroid eye drops for during and two days following HIDAC 3) myelosuppression

• Dosing:

  • ≤60 years receive 3000 mg/m2 intravenous every 12 h for a total of 6 doses days 1, 2, 3

  • 60–65 years receive 2000 mg/m2 intravenous every 12 h for a total of 6 doses days 1, 2, 3

  • 65–75 years receive 1500 mg/m2 intravenous every 12 h for a total of 6 doses days 1, 2, 3

  • >75 years (clinical discussion) but we may consider 1000 mg/m2 intravenous every 12 h for a total of 6 doses days 1, 2, 3

CALGB 10403 (Course I to V)

• Standard of care for adolescent/young adults with Philadelphia chromosome negative ALL (age 18-40)

  • Patients > 40 YO may receive if intensive asparaginase benefits outweigh risks

• Regimen contains induction, consolidation, intensification and maintenance phases

• Rituximab may be added to all B-cell ALL regimens if CD20+

Larson Protocol (CALGB 8811 or CALGB 9511) (Course I to V) 

• Standard of care for adults with philadelphia chromosome negative (B and T cell ALL) fit to receive (age 40+)

• Regimen contains induction, consolidation, intensification and maintenance phases

• Rituximab may be added to all B-cell ALL regimens if CD20+

Hyper-CVAD Part A and Hyper-CVAD Part B

• For Philadelphia chromosome positive ALL in combination with a tyrosine kinase inhibitor (ie: dasatinib or ponatinib)

• Also for Philadelphia chromosome negative ALL in those who cannot tolerate an asparaginase containing regimen

• Many dose modifications may be made to improve tolerability in older patients

  • See publication: Optimizing the use of the hyperCVAD regimen: Clinical vignettes and practical management 

• Part A pearls: day 4 doxorubicin and vincristine an be moved up to be given immediately following the last dose of cyclophosphamide to facilitate early discharge

  • Mesna can be discontinued early to facilitate early discharge

• Part B pearls: keep a close eye on retiming of chemotherapy, premeds, and leucovorin as the whole regimen often needs retiming due to delays in starting while awaiting urine alkalinization

  • See clinical pearls for methotrexate (link under construction)

Blinatumomab for R/R disease and Blinatumomab for MRD+ Disease

• Multiple indications for use:

  • Relapsed/refractory B-cell ALL patients post at least 1 salvage regimen or deemed unfit for intensive chemotherapy; must be CD19+

    • Patients with <50% blasts benefit more than those with >50% blasts

  • Measurable residual disease positive ALL

  • Consolidation in patients with measurable residual disease NEGATIVE ALL based on the ECOG 1910 trial

  • The dosing is different for R/R disease vs when used in consolidation for MRD+ or MRD- disease

• See guidelines for the treatment of cytokine release syndrome

R-CHOP 

• Standard of care

R-mini-CHOP

• For older or frail patients

R-CEOP 

• Standard of care if a contraindication to an anthracycline

MR-CHOP 

• Utilized if parenchymal CNS involvement and systemic disease

DA-R-EPOCH 

• Controversial standard for double hit lymphomas

  • t(8;14) and t(14;18) - c-myc and BCL2, respectively

• Used for primary mediastinal lymphoma

• Cycle 2+ dosing is based on patients absolute neutrophil count and platelet nadir

DA-R-EPOCH (HIV Lymphoma) 

• Starting doses are different than non-HIV lymphoma

  • Cyclophosphamide doses selected based on the patient's CD4 T-cell count

  • Dose escalations and de-escalations are different than non-HIV lymphoma

R-ICE, R-Gem-Ox, R-DHAOx, R-DHAP, R-ESHAP, R-GDP

• These regimens are used for R/R DLBCL 

• R-ICE and R-DHAP are used most frequently for patients with the intent of proceeding to auto-transplant

• R-Gem-Ox is used most frequently for patients who are not candidates of auto-transplant or patients with significant liver and/or renal dysfunction

• Regimens such as polotuzumab, bendamustine, rituximab (PBR), tafasitamab with lenalidomide, or loncastuximab are used as an outpatient

• No regimen listed above has shown superiority over another therefore cost and toxicity profile is used to select therapy

Most multiple myeloma treatment is done as an outpatient - below we have only highlighted regimens that would be seen on the inpatient side. 

VDT-PACE 

• Aggressive regimen for aggressive disease in patients that can tolerate. Given as a continuous infusion over 4 days

CyBorD

• Option for patients with severe renal dysfunction 

• May be used in patients that are relapsed who haven't received cyclophosphamide yet

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