Multiple myeloma treatment episodes in EPISODE. Creation logic
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Background
Drug data available in observational health databases can be abstracted on 4 principal levels: drug exposure (single drug administration or prescription), drug era (continuous drug administration or prescription), treatment regimen (drugs used in combination with fixed schedule), line of therapy (several regimens used consecutively united by one clinical intent). The first two levels exist in our OMOP common data model (CDM) datasets, and we need an effective way of capturing and storing lines and regimen.
Rules applied
Rules for Regimen building
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The first regimen starts as the first multiple myeloma (MM)s-specific drug exposure after or on the day of the first MM diagnosis (concept_id = 437233 Multiple myeloma)
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All MM-specific drugs (see appendix 1) within 30 days of a regimen start are considered part of same regimen (applicable to the first and subsequent regimen)
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The regimen ends if either:
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A new drug is added after the first 30 days
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Any drug from the first regimen is discontinued (not used for more than 90 days), note if other drugs are discontinued within 30 days of this event, the last event within these 30 days is considered the regimen end date.
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A new regimen starts as either
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The day after the previous regimen end
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Start of the new drug era, if there was gap between previous regimens
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Steps 2 – 4 are repeated until all drug eras of drugs of interest are covered
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Add CAR-T regimens. Currently the CAR-T events are divided into 3 groups (subject of a discussion):
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‘Apheresis Aph&CART’ – when both Apheresis procedure and CAR-T injection event are present in the data. Apheresis date is both start and end date of the regimen.
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CAR-T’: drug_exposure_start_date and drug_exposure_end_date are considered a regimen start and end date.
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‘Apheresis no CART’: Apheresis procedure is documented, but the CAR-T is not. Apheresis date is both start and end date of the regimen.
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Later both ‘Apheresis Aph&CART’ and ‘Apheresis no CART’ are mapped to the same Apheresis concept, but it’s reflected in episode_source_value, so we can track the Apheresis procedures which don’t have CAR-T infusion afterwards.
Apheresis concept_ids: 927059 “Chimeric antigen receptor T-cell (CAR-T) therapy; harvesting of blood-derived T lymphocytes for development of genetically modified autologous CAR-T cells, per day”
CAR-T codes are in Appendix 2.
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Add Transplant regimen. Transplant date is regimen_start_date as well as regimen_end_date. If two transplants are given within 180 days, only the first one is written into regimen. See the list of codes in appendix 3.
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Regimen source names are the names of drugs or procedures in alphabetical order
Lines of therapy rules
Regimens are combined into lines of therapy using the following rules:
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The regimen is marked as Maintenance therapy (will be used as a component of line of therapy) when:
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It’s ‘bortezomib’, ‘lenalidomide’, ‘thalidomide’ or ‘ixazomib’ monotherapy, and a previous regimen was polytherapy, and length of a previous regimen is more than 30 days, and length of a current regimen is more than 60 days, and the current regimen starts within 180 days after the previous regimen end.
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If It’s daratumumab monotherapy, apply rules from previous step, and additionally a previous regimen should include daratumumab
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It’s any drug monotherapy after the transplant that appears within a year after transplantation date.
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Regimens are grouped into line of therapy when they are:
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HSCT (autologous stem cell transplantation) and therapies that surround it, for example: bortezomib, lenalidomide (induction) then HSCT (autologous stem cell transplantation) then lenalidomide (maintenance); Melphalan (Pre-Transplant Conditioning) then HSCT.
- Sometimes drug data is missing, so we end up with incomplete therapies, for example bortezomib then HSCT, which requires lenalidomide as part of induction therapy
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Apheresis, anti-plasma cell treatment (cyclophosphamide, fludarabine or cyclophosphamide monotherapy), CAR-T
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Regimen and its corresponding maintenance therapy
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Addition of immunomodulatory (IMIDS = lenalidomide, pomalidomide, thalidomide) or proteasome inhibitor drugs (PI = bortezomib, carfilzomib, ixazomib) within the first 90 days of the previous regimen start, if the previous regimen doesn’t have the drugs from the same group (2 IMIDs or 2 PIs can’t be in the same line)
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The addition of lenalidomide in 1L to a line that already contained cyclophosphamide does not advance the line. Note: this addition must occur within 60 days of line start for this rule to be applied
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Most of the regimen are mapped to HemOnc concepts by matching ingredients and populate EPISODE.episode_object_concept_id, if there’s no corresponding concept, it was mapped to 0. Procedures are mapped as follows:
| Source Concept Name | Target Concept ID | Target Concept Name |
|---|---|---|
| HSCT | 4120445 | Hemopoietic stem cell transplant |
| CAR-T | 37557245 | Cellular therapy conditioning regimen |
| Apheresis Aph&CART | 4132856 | Apheresis |
| Apheresis no CART | 4132856 | Apheresis |
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Line of treatment concepts are mapped to 0, since HemOnc vocabulary doesn’t support lines, the value will be only stored in episode_source_value as names of regimen in their temporal order separated by ‘ then ‘.
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The start date of line of therapy is the start date of the first regimen, the end date of the line of therapy is the end date of the last regimen the line is made from.
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The line of treatment becomes a parent episode of treatment regimen
Mapping to the EPISODE table
| target column name | logic |
|---|---|
| episode_id | autoincrement |
| person_id | drug_era.person_id |
| episode_concept_id | For treatment regimen: 32531-- Treatment Regimen For lines of therapy: 32941 -- Cancer Drug Treatment -- can't find Line of Therapy episode concept. this is the closest we have now |
| episode_start_date | as described in the logic above |
| episode_start_datetime | NULL |
| episode_end_date | as described in the logic above |
| episode_end_datetime | NULL |
| episode_parent_id | episode_id of line of therapy which contains this regimen |
| episode_number | based on the order of dates of episodes/lines for a given patient |
| episode_object_concept_id | mapped HemOnc regimen concept or 0 for episodes, 0 for lines of treatment |
| episode_type_concept_id | 32880-- Standard algorithm |
| episode_source_value | for regimen: names of drugs or procedures in alphabetical order separated by ' ,' for lines of therapy: names of regimen in their temporal order separated by ‘ then ‘ |
| episode_source_concept_id | 0 |
Appendix.
Codesets used
- Chemo/immunotherapy drugs:
| concept_id | concept_name |
|---|---|
| 740067 | melphalan flufenamide |
| 741578 | teclistamab |
| 746340 | talquetamab |
| 746391 | elranatamab |
| 902725 | Doxorubicin pegylated liposomal |
| 902728 | Vincristine liposomal |
| 1301267 | melphalan |
| 1308290 | vincristine |
| 1310317 | cyclophosphamide |
| 1336825 | bortezomib |
| 1338512 | doxorubicin |
| 1350504 | etoposide |
| 1361191 | selinexor |
| 1395557 | fludarabine |
| 1397599 | cisplatin |
| 19026972 | lenalidomide |
| 19137042 | thalidomide |
| 35604032 | elotuzumab |
| 35604205 | venetoclax |
| 35605744 | daratumumab |
| 35606214 | ixazomib |
| 36849790 | 4-HYDROXYCYCLOPHOSPHAMIDE |
| 36858740 | FLUDARABINE F-18 |
| 37002419 | belantamab mafodotin |
| 37002429 | belantamab |
| 37498969 | isatuximab |
| 42873638 | carfilzomib |
| 43014237 | pomalidomide |
- CAR-T
| concept_id | concept_name |
|---|---|
| 739856 | lisocabtagene maraleucel |
| 779144 | ciltacabtagene autoleucel |
| 792737 | tisagenlecleucel |
| 792844 | axicabtagene ciloleucel |
| 36026868 | idecabtagene vicleucel |
| 37002369 | brexucabtagene autoleucel |
- Stem cell Transplant codes
| concept_id | concept_name |
|---|---|
| 2002363 | Autologous hematopoietic stem cell transplant without purging |
| 2002364 | Allogeneic hematopoietic stem cell transpant without purging |
| 2002365 | Cord blood stem cell transplant |
| 2002366 | Autologous hematopoietic stem cell transplant with purging |
| 2002367 | Allogeneic hematopoietic stem cell transplant with purging |
| 2721124 | Cord blood-derived stem-cell transplantation, allogeneic |
| 2721125 | Bone marrow or blood-derived stem cells (peripheral or umbilical), allogeneic or autologous, harvesting, transplantation, and related complications; including: pheresis and cell preparation/storage; marrow ablative therapy; drugs, supplies, hospitaliza… |
| 2785921 | Transfusion of Autologous Cord Blood Stem Cells into Central Artery, Percutaneous Approach (Deprecated) |
| 2785922 | Transfusion of Nonautologous Cord Blood Stem Cells into Central Artery, Percutaneous Approach (Deprecated) |
| 2785923 | Transfusion of Autologous Hematopoietic Stem Cells into Central Artery, Percutaneous Approach (Deprecated) |
| 2785924 | Transfusion of Nonautologous Hematopoietic Stem Cells into Central Artery, Percutaneous Approach (Deprecated) |
| 2788483 | Transfusion of Embryonic Stem Cells into Peripheral Vein, Open Approach (Deprecated) |
| 2788671 | Transfusion of Autologous Bone Marrow into Peripheral Vein, Open Approach (Deprecated) |
| 2788672 | Transfusion of Nonautologous Bone Marrow into Peripheral Vein, Open Approach (Deprecated) |
| 2788699 | Transfusion of Autologous Cord Blood Stem Cells into Peripheral Vein, Open Approach (Deprecated) |
| 2788700 | Transfusion of Nonautologous Cord Blood Stem Cells into Peripheral Vein, Open Approach (Deprecated) |
| 2788701 | Transfusion of Autologous Hematopoietic Stem Cells into Peripheral Vein, Open Approach (Deprecated) |
| 2788702 | Transfusion of Nonautologous Hematopoietic Stem Cells into Peripheral Vein, Open Approach (Deprecated) |
| 2788703 | Transfusion of Embryonic Stem Cells into Peripheral Vein, Percutaneous Approach |
| 2788704 | Transfusion of Autologous Bone Marrow into Peripheral Vein, Percutaneous Approach |
| 2788705 | Transfusion of Nonautologous Bone Marrow into Peripheral Vein, Percutaneous Approach (Deprecated) |
| 2788732 | Transfusion of Autologous Cord Blood Stem Cells into Peripheral Vein, Percutaneous Approach |
| 2788733 | Transfusion of Nonautologous Cord Blood Stem Cells into Peripheral Vein, Percutaneous Approach (Deprecated) |
| 2788734 | Transfusion of Autologous Hematopoietic Stem Cells into Peripheral Vein, Percutaneous Approach |
| 2788925 | Transfusion of Nonautologous Hematopoietic Stem Cells into Peripheral Vein, Percutaneous Approach (Deprecated) |
| 2788926 | Transfusion of Embryonic Stem Cells into Central Vein, Open Approach (Deprecated) |
| 2788927 | Transfusion of Autologous Bone Marrow into Central Vein, Open Approach (Deprecated) |
| 2788928 | Transfusion of Nonautologous Bone Marrow into Central Vein, Open Approach (Deprecated) |
| 2788955 | Transfusion of Autologous Cord Blood Stem Cells into Central Vein, Open Approach (Deprecated) |
| 2788956 | Transfusion of Nonautologous Cord Blood Stem Cells into Central Vein, Open Approach (Deprecated) |
| 2788957 | Transfusion of Autologous Hematopoietic Stem Cells into Central Vein, Open Approach (Deprecated) |
| 2788958 | Transfusion of Nonautologous Hematopoietic Stem Cells into Central Vein, Open Approach (Deprecated) |
| 2788959 | Transfusion of Embryonic Stem Cells into Central Vein, Percutaneous Approach |
| 2788960 | Transfusion of Autologous Bone Marrow into Central Vein, Percutaneous Approach |
| 2788961 | Transfusion of Nonautologous Bone Marrow into Central Vein, Percutaneous Approach (Deprecated) |
| 2788988 | Transfusion of Autologous Cord Blood Stem Cells into Central Vein, Percutaneous Approach |
| 2789176 | Transfusion of Nonautologous Cord Blood Stem Cells into Central Vein, Percutaneous Approach (Deprecated) |
| 2789177 | Transfusion of Autologous Hematopoietic Stem Cells into Central Vein, Percutaneous Approach |
| 2789178 | Transfusion of Nonautologous Hematopoietic Stem Cells into Central Vein, Percutaneous Approach (Deprecated) |
| 2789179 | Transfusion of Autologous Bone Marrow into Peripheral Artery, Open Approach (Deprecated) |
| 2789180 | Transfusion of Nonautologous Bone Marrow into Peripheral Artery, Open Approach (Deprecated) |
| 2789207 | Transfusion of Autologous Cord Blood Stem Cells into Peripheral Artery, Open Approach (Deprecated) |
| 2789208 | Transfusion of Nonautologous Cord Blood Stem Cells into Peripheral Artery, Open Approach (Deprecated) |
| 2789209 | Transfusion of Autologous Hematopoietic Stem Cells into Peripheral Artery, Open Approach (Deprecated) |
| 2789210 | Transfusion of Nonautologous Hematopoietic Stem Cells into Peripheral Artery, Open Approach (Deprecated) |
| 2789211 | Transfusion of Autologous Bone Marrow into Peripheral Artery, Percutaneous Approach (Deprecated) |
| 2789212 | Transfusion of Nonautologous Bone Marrow into Peripheral Artery, Percutaneous Approach (Deprecated) |
| 2789428 | Transfusion of Autologous Cord Blood Stem Cells into Peripheral Artery, Percutaneous Approach (Deprecated) |
| 2789429 | Transfusion of Nonautologous Cord Blood Stem Cells into Peripheral Artery, Percutaneous Approach (Deprecated) |
| 2789430 | Transfusion of Autologous Hematopoietic Stem Cells into Peripheral Artery, Percutaneous Approach (Deprecated) |
| 2789431 | Transfusion of Nonautologous Hematopoietic Stem Cells into Peripheral Artery, Percutaneous Approach (Deprecated) |
| 2789432 | Transfusion of Autologous Bone Marrow into Central Artery, Open Approach (Deprecated) |
| 2789433 | Transfusion of Nonautologous Bone Marrow into Central Artery, Open Approach (Deprecated) |
| 2789460 | Transfusion of Autologous Cord Blood Stem Cells into Central Artery, Open Approach (Deprecated) |
| 2789461 | Transfusion of Nonautologous Cord Blood Stem Cells into Central Artery, Open Approach (Deprecated) |
| 2789462 | Transfusion of Autologous Hematopoietic Stem Cells into Central Artery, Open Approach (Deprecated) |
| 2789463 | Transfusion of Nonautologous Hematopoietic Stem Cells into Central Artery, Open Approach (Deprecated) |
| 2789464 | Transfusion of Autologous Bone Marrow into Central Artery, Percutaneous Approach (Deprecated) |
| 2789465 | Transfusion of Nonautologous Bone Marrow into Central Artery, Percutaneous Approach (Deprecated) |
| 4028623 | Transplantation of bone marrow |
| 4059885 | Autologous bone marrow transplant without purging |
| 4081380 | Peripheral blood stem cell graft |
| 4083057 | Cord cell transfusion |
| 4120445 | Hemopoietic stem cell transplant |
| 4121104 | Syngeneic bone marrow transplant |
| 4122920 | T-cell depleted allogeneic bone marrow graft |
| 4125486 | Imperfect T-cell depleted allogeneic bone marrow graft |
| 4125487 | Allogeneic related bone marrow transplant |
| 4125488 | Allogeneic unrelated bone marrow transplant |
| 4139690 | Grafting of cord blood to bone marrow |
| 4142405 | Allograft of bone marrow from sibling donor |
| 4143404 | Allogeneic peripheral blood stem cell transplant |
| 4144157 | Autologous peripheral blood stem cell transplant |
| 4144882 | Allograft of bone marrow from matched unrelated donor |
| 4145532 | Allograft of cord blood to bone marrow |
| 4186582 | Autologous bone marrow transplant with purging |
| 4240337 | Autologous bone marrow transplant |
| 4242257 | Allogeneic bone marrow transplantation |
| 37152106 | High-dose chemotherapy with stem cell transplant |
| 40484034 | Grafting of bone marrow using allograft from unmatched unrelated donor |
| 40486968 | Allogeneic bone marrow transplantation with purging |
| 40492289 | Allogeneic bone marrow transplantation without purging |
| 44514755 | Other specified graft of bone marrow |
| 44515878 | Other specified graft of cord blood stem cells to bone marrow |
| 44783964 | Syngeneic peripheral blood stem cell transplantation |
| 44790154 | Allograft of bone marrow from haploidentical donor |
| 44793170 | Allograft of bone marrow from unmatched unrelated donor |
| 46271079 | Transplantation of autologous hematopoietic stem cell |